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• Tags: Academic Writing , Essay , Essay Writing

Writing an effective and impactful essay is crucial to your academic or professional success. Whether it’s getting into the college of your dreams or scoring high on a major assignment, writing a well-structured essay will help you achieve it all. But before you learn how to write an essay , you need to know its basic components.

In this article, we will understand what an essay is, how long it should be, and its different parts and types. We will also take a detailed look at relevant examples to better understand the essay structure.

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What is an essay?

An essay is a concise piece of nonfiction writing that aims to either inform the reader about a topic or argue a particular perspective. It can either be formal or informal in nature. Most academic essays are highly formal, whereas informal essays are commonly found in journal entries, social media, or even blog posts.

As we can see from this essay definition, the beauty of essays lies in their versatility. From the exploration of complex scientific concepts to the history and evolution of everyday objects, they can cover a vast range of topics.

How long is an essay?

The length of an essay can vary from a few hundred to several thousand words but typically falls between 500–5,000 words. However, there are exceptions to this norm, such as Joan Didion and David Sedaris who have written entire books of essays.

Let’s take a look at the different types of essays and their lengths with the help of the following table:

How many paragraphs are in an essay?

Typically, an essay has five paragraphs: an introduction, a conclusion, and three body paragraphs. However, there is no set rule about the number of paragraphs in an essay.

The number of paragraphs can vary depending on the type and scope of your essay. An expository or argumentative essay may require more body paragraphs to include all the necessary information, whereas a narrative essay may need fewer.

Structure of an essay

To enhance the coherence and readability of your essay, it’s important to follow certain rules regarding the structure. Take a look:

1. Arrange your information from the most simple to the most complex bits. You can start the body paragraph off with a general statement and then move on to specifics.

2. Provide the necessary background information at the beginning of your essay to give the reader the context behind your thesis statement.

3. Select topic statements that provide value, more information, or evidence for your thesis statement.

There are also various essay structures , such as the compare and contrast structure, chronological structure, problem method solution structure, and signposting structure that you can follow to create an organized and impactful essay.

Parts of an essay

An impactful, well-structured essay comes down to three important parts: the introduction, body, and conclusion.

1. The introduction sets the stage for your essay and is typically a paragraph long. It should grab the reader’s attention and give them a clear idea of what your essay will be about.

2. The body is where you dive deeper into your topic and present your arguments and evidence. It usually consists of two paragraphs, but this can vary depending on the type of essay you’re writing.

3. The conclusion brings your essay to a close and is typically one paragraph long. It should summarize the main points of the essay and leave the reader with something to think about.

The length of your paragraphs can vary depending on the type of essay you’re writing. So, make sure you take the time to plan out your essay structure so each section flows smoothly into the next.

Introduction

When it comes to writing an essay, the introduction is a critical component that sets the tone for the entire piece. A well-crafted introduction not only grabs the reader’s attention but also provides them with a clear understanding of what the essay is all about. An essay editor can help you achieve this, but it’s best to know the brief yourself!

Let’s take a look at how to write an attractive and informative introductory paragraph.

1. Construct an attractive hook

To grab the reader’s attention, an opening statement or hook is crucial. This can be achieved by incorporating a surprising statistic, a shocking fact, or an interesting anecdote into the beginning of your piece.

For example, if you’re writing an essay about water conservation you can begin your essay with, “Clean drinking water, a fundamental human need, remains out of reach for more than one billion people worldwide. It deprives them of a basic human right and jeopardizes their health and wellbeing.”

2. Provide sufficient context or background information

An effective introduction should begin with a brief description or background of your topic. This will help provide context and set the stage for your discussion.

For example, if you’re writing an essay about climate change, you start by describing the current state of the planet and the impact that human activity is having on it.

3. Construct a well-rounded and comprehensive thesis statement

A good introduction should also include the main message or thesis statement of your essay. This is the central argument that you’ll be making throughout the piece. It should be clear, concise, and ideally placed toward the end of the introduction.

By including these elements in your introduction, you’ll be setting yourself up for success in the rest of your essay.

Let’s take a look at an example.

Essay introduction example

• Background information
• Thesis statement

The Wright Brothers’ invention of the airplane in 1903 revolutionized the way humans travel and explore the world. Prior to this invention, transportation relied on trains, boats, and cars, which limited the distance and speed of travel. However, the airplane made air travel a reality, allowing people to reach far-off destinations in mere hours. This breakthrough paved the way for modern-day air travel, transforming the world into a smaller, more connected place. In this essay, we will explore the impact of the Wright Brothers’ invention on modern-day travel, including the growth of the aviation industry, increased accessibility of air travel to the general public, and the economic and cultural benefits of air travel.

Body paragraphs

You can persuade your readers and make your thesis statement compelling by providing evidence, examples, and logical reasoning. To write a fool-proof and authoritative essay, you need to provide multiple well-structured, substantial arguments.

Let’s take a look at how this can be done:

1. Write a topic sentence for each paragraph

The beginning of each of your body paragraphs should contain the main arguments that you’d like to address. They should provide ground for your thesis statement and make it well-rounded. You can arrange these arguments in several formats depending on the type of essay you’re writing.

2. Provide the supporting information

The next point of your body paragraph should provide supporting information to back up your main argument. Depending on the type of essay, you can elaborate on your main argument with the help of relevant statistics, key information, examples, or even personal anecdotes.

3. Analyze the supporting information

After providing relevant details and supporting information, it is important to analyze it and link it back to your main argument.

4. Create a smooth transition to the next paragraph

End one body paragraph with a smooth transition to the next. There are many ways in which this can be done, but the most common way is to give a gist of your main argument along with the supporting information with transitory words such as “however” “in addition to” “therefore”.

Here’s an example of a body paragraph.

Essay body paragraph example

• Topic sentence
• Supporting information
• Analysis of the information
• Smooth transition to the next paragraph

The Wright Brothers’ invention of the airplane revolutionized air travel. They achieved the first-ever successful powered flight with the Wright Flyer in 1903, after years of conducting experiments and studying flight principles. Despite their first flight lasting only 12 seconds, it was a significant milestone that paved the way for modern aviation. The Wright Brothers’ success can be attributed to their systematic approach to problem-solving, which included numerous experiments with gliders, the development of a wind tunnel to test their designs, and meticulous analysis and recording of their results. Their dedication and ingenuity forever changed the way we travel, making modern aviation possible.

A powerful concluding statement separates a good essay from a brilliant one. To create a powerful conclusion, you need to start with a strong foundation.

Let’s take a look at how to construct an impactful concluding statement.

1. Restructure your thesis statement

To conclude your essay effectively, don’t just restate your thesis statement. Instead, use what you’ve learned throughout your essay and modify your thesis statement accordingly. This will help you create a conclusion that ties together all of the arguments you’ve presented.

2. Summarize the main points of your essay

The next point of your conclusion consists of a summary of the main arguments of your essay. It is crucial to effectively summarize the gist of your essay into one, well-structured paragraph.

3. Create a lasting impression with your concluding statement

Conclude your essay by including a key takeaway, or a powerful statement that creates a lasting impression on the reader. This can include the broader implications or consequences of your essay topic.

Here’s an example of a concluding paragraph.

Essay conclusion example

• Restated thesis statement
• Summary of the main points
• Broader implications of the thesis statement

The Wright Brothers’ invention of the airplane forever changed history by paving the way for modern aviation and countless aerospace advancements. Their persistence, innovation, and dedication to problem-solving led to the first successful powered flight in 1903, sparking a revolution in transportation that transformed the world. Today, air travel remains an integral part of our globalized society, highlighting the undeniable impact of the Wright Brothers’ contribution to human civilization.

Types of essays

Most essays are derived from the combination or variation of these four main types of essays . let’s take a closer look at these types.

1. Narrative essay

A narrative essay is a type of writing that involves telling a story, often based on personal experiences. It is a form of creative nonfiction that allows you to use storytelling techniques to convey a message or a theme.

2. Descriptive essay

A descriptive essay aims to provide an immersive experience for the reader by using sensory descriptors. Unlike a narrative essay, which tells a story, a descriptive essay has a narrower scope and focuses on one particular aspect of a story.

3. Argumentative essays

An argumentative essay is a type of essay that aims to persuade the reader to adopt a particular stance based on factual evidence and is one of the most common forms of college essays.

4. Expository essays

An expository essay is a common format used in school and college exams to assess your understanding of a specific topic. The purpose of an expository essay is to present and explore a topic thoroughly without taking any particular stance or expressing personal opinions.

While this article demonstrates what is an essay and describes its types, you may also have other doubts. As experts who provide essay editing and proofreading services , we’re here to help. 

Our team has created a list of resources to clarify any doubts about writing essays. Keep reading to write engaging and well-organized essays!

• How to Write an Essay in 8 Simple Steps
• How to Write an Essay Header
• How to Write an Essay Outline

Frequently Asked Questions

What is the difference between an argumentative and an expository essay, what is the difference between a narrative and a descriptive essay, what is an essay format, what is the meaning of essay, what is the purpose of writing an essay.

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Discussion essays Considering both sides of the argument

Discussion essays are a common form of academic writing. This page gives information on what a discussion essay is and how to structure this type of essay. Some vocabulary for discussion essays is also given, and there is an example discussion essay on the topic of studying overseas.

What are discussion essays?

Many essay titles require you to examine both sides of a situation and to conclude by saying which side you favour. These are known as discussion or for and against essays. In this sense, the academic meaning of the word discuss is similar to its everyday meaning, of two people talking about a topic from different sides. For a discussion essay, a balanced view is normally essential. This makes discussion essays distinct from persuasion essays , for which only one side of the argument is given. When writing a discussion essay, it is important to ensure that facts and opinions are clearly separated. Often you will examine what other people have already said on the same subject and include this information using paraphrasing and summarising skills, as well as correct citations .

The following are examples of discussion essay topics.

• Examine the arguments for and against capital punishment.
• Schools should teach children not only academic subjects but also important life skills. Discuss.
• What are the advantages and disadvantages of technology in the classroom?

Although the structure of a discussion essay may vary according to length and subject, there are several components which most discussion essays have in common. In addition to general statements and thesis statement which all good essay introductions contain, the position of the writer will often be stated, along with relevant definitions . The main body will examine arguments for (in one or more paragraphs) and arguments against (also in one or more paragraphs). The conclusion will contain a summary of the main points, and will often conclude with recommendations , based on what you think are the most important ideas in the essay. The conclusion may also contain your opinion on the topic, also based on the preceding evidence.

An overview of this structure is given in the diagram below.

Discussion vocabulary

When summarising the stages in a discussion or in presenting your arguments, it can be useful to mark the order of the items or degrees of importance. The following words and phrases can be used.

• First..., First of all..., The most important...
• Second..., In the second place...
• Finally..., Lastly...

The following can be used when introducing your opinion.

• There is no doubt that...
• I believe that...
• One of the main arguments in favour of/against X is that...

It is important in English writing, including academic writing, to use synonyms rather than repeating the same word. The following are useful synonyms for 'advantage' and 'disadvantage'.

• advantage: benefit, a positive aspect/feature, pro (informal)
• disadvantage: drawback, a negative aspect/feature, con (informal)

Example essay

Below is an example discussion essay. Click on the different areas (in the shaded boxes to the right) to highlight the different structural aspects in this essay.

Title: An increasing number of students are going overseas for tertiary education. To what extent does this overseas study benefit the students?

Most people spend around fifteen years of their life in education, from primary school to university study. In the past, students only had the opportunity to study in their own country. Nowadays, however, it is increasingly easy to study overseas, especially at tertiary level. Tertiary education, also called post-secondary education, is the period of study spent at university. As the final aspect of schooling before a person begins their working life, it is arguably the most important stage of their education. While there are some undoubted benefits of this trend, such as the language environment and improved employment prospects , there is also a significant disadvantage, namely the high cost . The first and most important advantage of overseas study is the language learning environment. Students studying overseas will not only have to cope with the local language for their study, but will also have to use it outside the classroom for their everyday life. These factors should make it relatively easy for such students to advance their language abilities. Another important benefit is employability. Increasing globalisation means that there are more multinational companies setting up offices in all major countries. These companies will need employees who have a variety of skills, including the fluency in more than one language. Students who have studied abroad should find it much easier to obtain a job in this kind of company. There are, however, some disadvantages to overseas study which must be considered, the most notable of which is the expense. In addition to the cost of travel, which in itself is not inconsiderable, overseas students are required to pay tuition fees which are usually much higher than those of local students. Added to this is the cost of living, which is often much higher than in the students' own country. Although scholarships may be available for overseas students, there are usually very few of these, most of which will only cover a fraction of the cost. Overseas study therefore constitutes a considerable expense. In summary, studying abroad has some clear advantages, including the language environment and increased chances of employment , in addition to the main drawback, the heavy financial burden . I believe that this experience is worthwhile for those students whose families can readily afford the expense. Students without such strong financial support should consider carefully whether the high cost outweighs the benefits to be gained.

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Below is a checklist for discussion essays. Use it to check your own writing, or get a peer (another student) to help you.

Bailey, S. (2000). Academic Writing. Abingdon: RoutledgeFalmer

Cox, K. and D. Hill (2004). EAP now! Frenchs Forest: Pearson Education Australia

Jordan, R.R. (1999). Academic Writing Course. Cambridge: CUP

Roberts R., J. Gokanda, & A. Preshous (2004). IELTS Foundation. Oxford: Macmillian

Next section

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Author: Sheldon Smith    ‖    Last modified: 16 January 2022.

Sheldon Smith is the founder and editor of EAPFoundation.com. He has been teaching English for Academic Purposes since 2004. Find out more about him in the about section and connect with him on Twitter , Facebook and LinkedIn .

Compare & contrast essays examine the similarities of two or more objects, and the differences.

Cause & effect essays consider the reasons (or causes) for something, then discuss the results (or effects).

Discussion essays require you to examine both sides of a situation and to conclude by saying which side you favour.

Problem-solution essays are a sub-type of SPSE essays (Situation, Problem, Solution, Evaluation).

Transition signals are useful in achieving good cohesion and coherence in your writing.

Reporting verbs are used to link your in-text citations to the information cited.

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How to write a character analysis essay, basic essay structure: how to build it.

Writing a well-structured essay is like building a house: you need a solid foundation, sturdy walls, and a roof to complete it. A well-organized essay helps your ideas flow smoothly and makes it easier for readers to follow your argument. Plus, it shows that you’ve put thought into your work, making it more convincing and enjoyable to read.

So, what does a good essay structure look like? Whether you’re writing a narrative, descriptive, expository, or persuasive essay, following this structure will help you stay organized and make your writing more impactful. Let’s dive in and learn how to put it all together!

How to Structure an Essay

Imagine you’re building a house. You need a solid foundation, walls, and a roof to make it stand. Writing an essay is similar. It requires a good structure to hold your ideas together and make your argument clear. Let’s break down the go-to essay structure to help you get started.

First, you need an introduction that grabs the reader’s attention. Start with an engaging opening sentence that makes your reader want to keep going. This could be a surprising fact, a question, or a bold statement. Then, provide some background information to set the context or give a brief overview of the topic. Finally, end your introduction with a thesis statement that clearly presents the main argument or purpose of your essay.

Next, you have the body paragraphs . Each paragraph should begin with a topic sentence that introduces the main idea. Follow this with supporting details, which can be evidence, examples, or explanations that back up your point. It’s important to keep your ideas clear and logical. Also, use transitions to smoothly link each paragraph to the next, helping the reader follow your argument effortlessly.

Lastly, your conclusion ties everything together. Start by restating your thesis in different words to reinforce your main argument. Then, summarize the key points you discussed in the body paragraphs. This helps remind the reader of the journey they’ve taken through your essay. Finally, end with a closing statement or call to action that leaves a lasting impression. This could be a thought-provoking comment, a suggestion for further research, or a call to action based on your argument.

Remember, the introduction sets the stage, the body paragraphs build the argument, and the conclusion wraps it all up.

With practice, you’ll find that this go-to structure makes essay writing much easier and more effective.

Basic Essay Structure for Different Types of Essays

Writing essays becomes simpler when you understand the structure. Here, we’ll look at five common types: narrative, descriptive, expository, persuasive, and comparative essays. Each has unique characteristics and serves a specific purpose. I’ll also include an example of how to structure the main body for each type.

Narrative Essay

A narrative essay tells a story from the author’s perspective. It aims to engage the reader by making the story interesting and relatable.

Example Structure:

• Introduction : Set the scene and introduce the main character.
• Body Paragraph 1 : Describe the beginning of the story (setting, characters).
• Body Paragraph 2 : Describe the main event or conflict.
• Body Paragraph 3 : Describe the climax of the story.
• Conclusion : Describe the resolution and the lesson learned.

Descriptive Essay

A descriptive essay paints a picture with words. It aims to describe a person, place, object, or event so vividly that the reader can visualize it.

• Introduction : Introduce the subject you will describe.
• Body Paragraph 1 : Describe the subject using sight (what it looks like).
• Body Paragraph 2 : Describe the subject using sound (what it sounds like).
• Body Paragraph 3 : Describe the subject using smell, touch, and taste (if applicable).
• Conclusion : Summarize the main points and highlight the overall impression.

Expository Essay

An expository essay explains or informs. It provides a balanced analysis of a topic, using facts, statistics, and examples.

• Introduction : Present the topic and state the thesis.
• Body Paragraph 1 : Explain the first main idea with supporting facts and examples.
• Body Paragraph 2 : Explain the second main idea with supporting facts and examples.
• Body Paragraph 3 : Explain the third main idea with supporting facts and examples.
• Conclusion : Summarize the main points and restate the thesis.

Persuasive Essay

A persuasive essay aims to convince the reader to accept a particular viewpoint or take a specific action. It uses logic, reason, and emotion to build a compelling argument.

• Introduction : Introduce the topic and state your position.
• Body Paragraph 1 : Present the first supporting argument with evidence.
• Body Paragraph 2 : Present the second supporting argument with evidence.
• Body Paragraph 3 : Present the third supporting argument with evidence.
• Body Paragraph 4 : Address a counterargument and refute it.
• Conclusion : Summarize the arguments and reinforce your position.

Comparative Essay

A comparative essay examines the similarities and differences between two or more subjects. It helps the reader understand the subjects better by comparing them.

• Introduction : Introduce the subjects and state the basis for comparison.
• Body Paragraph 1 : Compare the first point of similarity or difference between the subjects.
• Body Paragraph 2 : Compare the second point of similarity or difference between the subjects.
• Body Paragraph 3 : Compare the third point of similarity or difference between the subjects.
• Conclusion : Summarize the comparisons and highlight the overall insights.

Now, you can effectively organize your essays and make your writing clear and engaging. Each type of essay has its unique features, so choose the one that best fits your topic and purpose.

How to Organize an Essay with Structural Transition Words

Using transitional words is like putting up road signs for your reader. These words guide them through your essay, making it easier to follow your thoughts and arguments. They help in creating a smooth flow, making your writing more engaging and coherent. Let’s dive into different types of transitional words and how they can be used effectively.

👋 Introduction to Body

When you transition from the introduction to the body of your essay, you need words that signal the beginning of your main discussion. These words help to seamlessly connect the introduction to the detailed points you will cover.

For instance, words like “ Firstly ,” “ To begin with ,” and “ Initially ” are perfect for starting your body paragraphs. They let the reader know that you are moving from the introductory context to the main points. For example, you might say, “Firstly, it’s important to understand the historical context of the issue.” Or, “To begin with, let’s explore the primary causes of the conflict.” These words set the stage for detailed analysis and help the reader transition smoothly from the general introduction to specific arguments.

➕ Adding Information

When you need to add more information or points to your argument, transitional words come in handy. These words indicate that there is more to say on the topic, building on what has already been mentioned.

Words like “ Furthermore ,” “ Moreover ,” and “ Additionally ” are great for adding information. For example, “Furthermore, recent studies support this claim,” or “Moreover, this approach has been widely adopted in several countries.” By using these words, you show that you are expanding on your previous points, making your argument more comprehensive and convincing.

✅ Providing Examples

To illustrate your points more clearly, providing examples is absolutely necessary. Transitional words help introduce these examples smoothly, showing the reader that you are giving concrete evidence to support your claims.

Examples of such words include “ For example ,” “ For instance ,” and “ Such as .” You might write, “For example, many schools have implemented this program successfully,” or “For instance, in the case of renewable energy, solar power has shown remarkable potential.” These words prepare the reader for specific details that back up your general statements, making your argument stronger.

☀️❄️ Contrasting Information

Sometimes, you need to present contrasting information to show different perspectives or to highlight an exception to the rule. Transitional words help indicate a shift from one idea to a contrasting one.

Words like “ However ,” “ On the other hand ,” and “ Conversely ” are ideal for this purpose. For example, “However, not all experts agree with this view,” or “On the other hand, there are significant challenges to this approach.” These words signal to the reader that you are about to present a different angle, helping them to understand the complexity of the issue.

🔀 Showing Cause and Effect

To explain the relationship between actions and outcomes, cause-and-effect transitional words are essential. They help you link causes to their effects clearly and logically.

Words such as “ Therefore ,” “ Consequently ,” and “ As a result ” are perfect for this. You might say, “Therefore, it is clear that immediate action is necessary,” or “Consequently, the policy had to be revised.” These words make it easy for the reader to follow the logical progression of your argument, showing how one idea leads to another.

📍 Summarizing/Concluding

In the conclusion of your essay, you need transitional words that help you summarize your main points and bring your argument to a close. These words signal to the reader that you are wrapping up your discussion.

Examples include “ In conclusion ,” “ To summarize ,” and “ Ultimately .” For example, “In conclusion, the evidence strongly supports the need for policy change,” or “To summarize, the key factors influencing this issue have been thoroughly examined.” These words help you succinctly tie together your main points and leave the reader with a clear understanding of your argument.

Tips for Writing a Structure of an Essay

Writing a well-structured essay is like building a strong bridge that connects your ideas seamlessly. Let’s dive into some tips that can help you create a clear and effective essay structure.

Think of an outline as your essay’s roadmap. Before you start writing, take some time to outline your main points. This will give you a clear direction and keep you on track. Start with your introduction, list out the key points you’ll cover in the body, and jot down ideas for your conclusion. Outlining helps you organize your thoughts and makes the writing process smoother.

Each paragraph in your essay should focus on one main idea. Begin with a topic sentence that clearly states this idea. The rest of the paragraph should provide evidence, examples, or explanations that support the topic sentence. This keeps your writing focused and makes it easier for the reader to follow your argument. For example, if you’re writing about the benefits of exercise, one paragraph might focus on physical health benefits, while another might discuss mental health improvements.

Transitions are the glue that holds your essay together. They help you move smoothly from one idea to the next, ensuring your essay flows well. Words like “Firstly,” “Additionally,” “However,” and “In conclusion” guide your reader through your essay. These transitions make your writing more coherent and help emphasize the relationships between your ideas.

A well-balanced essay is easy to read and understand. Make sure your paragraphs are roughly the same length and provide a balanced amount of information. Avoid cramming too much information into one paragraph or making another too short. Each paragraph should be clear, focused, and contribute to your overall argument. This balance keeps your essay well-organized and engaging.

Once you’ve finished writing, take the time to proofread your essay. Look for structural consistency: Are your paragraphs in a logical order? Do your transitions make sense? Is each paragraph focused on a single main idea? Proofreading helps you catch any inconsistencies or areas that might confuse your reader. It’s also a good time to check for clarity. Make sure your ideas are clearly expressed and easy to understand.

Writing a structured essay doesn’t have to be complicated. By outlining your essay, ensuring each paragraph has a clear main idea, using transitions, keeping paragraphs balanced, and proofreading for consistency and clarity, you can create an essay that is both engaging and easy to follow. Practice these tips, and you’ll become more confident in your essay writing skills. Happy writing!

How should I structure an essay?

Structuring an essay involves three main parts: the introduction, the body, and the conclusion. Start with an engaging introduction that includes a hook, background information, and a clear thesis statement. Then, develop your main ideas in body paragraphs, each starting with a topic sentence and supported by evidence. Finally, wrap up your essay with a conclusion that restates the thesis, summarizes key points, and leaves the reader with a final thought or call to action.

What are the 3 major parts of essay structure?

The three major parts of an essay structure are the introduction, body, and conclusion. The introduction sets the stage by introducing the topic and stating the thesis. The body is the main section where you develop your ideas and arguments, usually in several paragraphs. The conclusion ties everything together, restating the thesis and summarizing the main points, providing closure to the discussion.

What is the 5 point structure to an essay?

The 5 point structure to an essay includes:

• Introduction : Hook, background information, and thesis statement.
• Body Paragraph 1 : First main point with supporting evidence.
• Body Paragraph 2 : Second main point with supporting evidence.
• Body Paragraph 3 : Third main point with supporting evidence.
• Conclusion : Restate thesis, summarize key points, and final thought.

This structure helps organize your essay in a clear, logical manner, making it easier for the reader to follow and understand your argument.

What is an example of essay structure?

An example of an essay structure might look like this:

Introduction : “Education is essential for personal and societal growth. This essay will discuss the importance of education in developing critical thinking skills, promoting social equality, and fostering economic development.”

Body Paragraph 1 : “Firstly, education plays a crucial role in developing critical thinking skills. Students learn to analyze information, evaluate arguments, and solve problems creatively. For instance, critical thinking is emphasized in subjects like mathematics and science.”

Body Paragraph 2 : “Moreover, education promotes social equality by providing opportunities for all individuals, regardless of their background. Public schooling systems aim to offer equal access to quality education, helping to bridge the gap between different social classes.”

Body Paragraph 3 : “Finally, education fosters economic development by creating a skilled workforce. Educated individuals are more likely to find employment, contribute to innovation, and drive economic growth. For example, countries with higher education levels often have stronger economies.”

Conclusion : “In conclusion, education is vital for developing critical thinking skills, promoting social equality, and fostering economic development. Investing in education is essential for creating a better future for individuals and society as a whole.”

This structure ensures that your essay is well-organized and that each point is clearly presented and supported.

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Study Toolbox: Structure of an Academic Essay

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Essays allow you to demonstrate your in-depth knowledge of a topic based on research and reading.  The focus of an essay is to develop an argument or analyse ideas rather than write a description. 

An essay is written in paragraphs and has a set structure of an introduction, a body and a conclusion.

Structure of an academic essay

• Introduction
• Reference List

The introduction begins with a general statement that establishes the focus of the essay.  It then outlines the main ideas of the essay and the order in which they will be discussed.  

The body contains a number of paragraphs that link together to present a strong argument or analysis of the topic.  There should be one main point per paragraph.

Every paragraph starts with a topic sentence which states the main idea of that paragraph.  This is followed by supporting sentences that fully explain and expand on the main idea raised in the topic sentence.  This explanation needs to be supported by evidence including quotes, examples or statistics.  The paragraph is finished with a concluding sentence that summarises the paragraph.  

The purpose of the conclusion is to summarise the main points and draw them together to make a final comment on the topic presented in the essay.  Do not introduce any new information or include quotes in your conclusion.

Your reference list includes the full reference for every source cited within your essay.  SIT requires APA 7th edition for referencing, so make sure all your references are formatted correctly. 

For assistance with referencing check out the EndNote 20 Guide / APA Referencing Guide .

Essay Layout

Introduction:

• A general statement that establishes the focus of the essay.
• Outline the main ideas of the essay and the order in which they will be discussed.

Each paragraph in the body should have:

• A topic sentence that states the main point of the paragraph.
• An explanation and/or expansion of the main point.
• Evidence to support the main point.

Conclusion:

• Summarise the main points.
• Make a final comment on the argument or concept presented in the essay.

Essay Handbook

• Te Pukenga | Southern Institute of Technology Essay Writing Handbook This is the official academic writing guide for SIT. This guide provides detailed information on all aspects of essay writing.

Assignment Writing

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Video credited to University of South Australia.

University of South Australia. (2021, September 28). Study help: Essays [Video]. YouTube. https://www.youtube.com/watch?v=xLhdrbBYEuA

University of South Australia. (2021, September 28).  Study help: Report writing  [Video]. YouTube.  https://www.youtube.com/watch?v=pPK4w-FhgRA

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How to Write a Discussion Essay

Last Updated: June 27, 2023 Fact Checked

This article was co-authored by Jake Adams . Jake Adams is an academic tutor and the owner of Simplifi EDU, a Santa Monica, California based online tutoring business offering learning resources and online tutors for academic subjects K-College, SAT & ACT prep, and college admissions applications. With over 14 years of professional tutoring experience, Jake is dedicated to providing his clients the very best online tutoring experience and access to a network of excellent undergraduate and graduate-level tutors from top colleges all over the nation. Jake holds a BS in International Business and Marketing from Pepperdine University. There are 14 references cited in this article, which can be found at the bottom of the page. This article has been fact-checked, ensuring the accuracy of any cited facts and confirming the authority of its sources. This article has been viewed 446,020 times.

Discussion Essay Outline and Example

Planning Your Essay

• For instance, maybe the question is, "Immigration has been a heated topic on the national level for many years. With issues like the DREAM Act and President Trump's stances on policy, it's likely to remain a central issue. Using authoritative resources to back up your argument, take a stance on immigration policy, establishing whether you think it should be more or less strict and why."
• You can establish that the main topic is immigration policy from the sentence, "Take a stance on immigration policy."
• If you're having trouble understanding the question, don't be afraid to talk to the professor. They can help you better understand what they're asking for.

• If your essay will be based off a discussion had in class, ask your instructor if you can use class notes as a primary source.
• Look for respected news sources, as well as websites with ".edu" and ".gov" extensions.
• You may need to look up information on the DREAM Act or President Trump's policies to help you understand the question, for example. For this part, you don't need to take extensive notes, as you're just trying to get a feel for the subject.

• If you were given a text to base your essay on, make sure that text has enough evidence to support your chosen position.

• Use Roman numerals on your page to mark your main ideas. Write a main point by each Roman numeral. You should only cover 3 to 4 main points in a relatively short essay, such as one that's 3 to 5 pages.

• Your main sources should be books or ebooks, journal articles from academic journals, and credible websites. You can also use high quality news articles if they're applicable to your topic.

• For a book, you should include the author's name, the editor's name (if applicable), the title of the book, the publication year, the publication city, the edition, and the title of the book chapter in an anthology by multiple authors.
• For a journal, include the author's name, the journal title, the article title, the digital object identifier (DOI), the ISSN, the publication date, the volume (if applicable), the issue (if applicable), and the page numbers for the journal article.
• If you're searching in a database, you can often ask the database to save this information for you, but you should include identifiers on your notes.

• For example, if one of your main points is "Immigration increases diversity," some of your points underneath might be "Brings in new cuisines," and "Brings in new art."
• Find examples from your research, and add notes to each point to fill them in.

Writing the Introduction

• For an example or anecdote, start by telling a short story about something relevant to your topic. For instance, you might write the following for an essay on immigration, "When I was 4-years-old, my parents told me we were going on a long trip. After a bus ride, we spent nights walking, my dad carrying me most of the way. One day, we crossed a river. That day marked our first day in our new country."

• For example, you might write, "Immigration is a highly-debated issue. It is controversial because some people fear how it affects the resources of the country the people are immigrating to, while others believe the improved quality of life for immigrants is what’s most important."

• For instance, your thesis statement might be, "Immigration is good for the country because it increases diversity, infuses the country with new talent, and broadens the population's perspective, and it should be encouraged with a few basic safeguards in place."

Composing the Body of Your Essay

• For instance, if you're writing a short research paper, one paragraph might be your main point "Immigration increases diversity," where you cover all your bullet points in that paragraph.
• If you're digging deeper, you might create a section about diversity, and then use a paragraph to cover "brings in new cuisines," another to cover "brings in new art," and so on.

• Try not to set up a "straw man" argument, where you don't give the other side a fair chance. You should be able to support your position without purposefully creating a weak position on the other side.

• For instance, maybe you want to transition between a section about increasing diversity to one about bringing in new talent. You might write a sentence like, "Increasing diversity in our country doesn't just bring in new cuisines and art, it also brings in hard workers that have fresh perspectives on old problems in the workforce."

• You can paraphrase other ideas or use direct quotes, but only use a direct quote if the author said something in a unique way. Otherwise, put it in your own words.
• You may want to begin body paragraphs with a quote from a relevant source. Then, explain or provide commentary on the quote and show how it supports your position.
• You can also use statistics to back up your research. For instance, if one of your arguments is that immigration doesn't increase crime, use statistics to back that up.

Concluding Your Essay

• For instance, you might write, "A truly great country is one that celebrates differences and welcomes new ideas and perspectives. While immigration has some negative effects on a country, overall, allowing people from other countries to come in helps to spark new ideas and make the country a better and more interesting place to live. Rather than being a drain on society, immigrants are motivated to work hard and our citizens can only benefit from listening to their perspectives."

• Once you have the flow down, read it again to check for grammatical mistakes and typos. It can help to read it aloud, as it slows you down and forces you to read every word.

Expert Q&A

• Remember you can't research forever. Often, the research stage absorbs a student so fully that the upcoming submission date seems unimportant. Make sure to leave yourself at least a few days to write your essay. Thanks Helpful 1 Not Helpful 0

You Might Also Like

• ↑ Jake Adams. Academic Tutor & Test Prep Specialist. Expert Interview. 20 May 2020.
• ↑ https://student.unsw.edu.au/answering-assignment-questions
• ↑ https://student.unsw.edu.au/essay-and-assignment-planning
• ↑ https://opentextbc.ca/writingforsuccess/chapter/chapter-11-developing-a-convincing-argument/
• ↑ https://student.unsw.edu.au/organising-your-ideas
• ↑ https://writingcenter.unc.edu/tips-and-tools/introductions/
• ↑ https://www.umgc.edu/current-students/learning-resources/writing-center/writing-resources/parts-of-an-essay/essay-introductions
• ↑ https://wts.indiana.edu/writing-guides/how-to-write-a-thesis-statement.html
• ↑ https://www.student.unsw.edu.au/writing-your-essay
• ↑ https://owl.purdue.edu/owl/general_writing/academic_writing/establishing_arguments/organizing_your_argument.html
• ↑ https://owl.purdue.edu/owl/general_writing/academic_writing/establishing_arguments/research_and_evidence.html
• ↑ https://writingcenter.unc.edu/tips-and-tools/conclusions/
• ↑ https://libguides.usc.edu/writingguide/conclusion
• ↑ https://writingcenter.unc.edu/tips-and-tools/editing-and-proofreading/

About This Article

To write a discussion essay, start by taking a side on the issue you're writing about, like "Immigration is good for the country." Then, outline the main points that made you decide to take that position and do research to find evidence that backs them up. Look for credible sources that can help you make your argument, and don't forget to cite them. Then, when you're writing your essay, devote 1 paragraph to each main point and include your evidence. For help writing the introduction and conclusion to your essay, scroll down! Did this summary help you? Yes No

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How To Plan & Write IELTS Discussion Essays

Students can find it difficult to identify IELTS discussion essays and often confuse them with either opinion essays or advantage and disadvantage essays.

This is one of the issues I’ll be covering in this lesson. I’m also going to show you how to plan and write discussion essays step-by-step.

Here’s what we’ll be covering:

• Identifying IELTS discussion essays 
• 3 Common mistakes
• Essay structure
• How to plan
• How to write an introduction
• How to write main body paragraphs
• How to write a conclusion

Want to watch and listen to this lesson?

Click on this video.

Click the links to see lessons on each of these Task 2 essay writing topics. 

Once you understand the process, practice on past questions. Take your time at first and gradually speed up until you can plan and write an essay of at least 250 words in the 40 minutes allowed in the exam.

The Question

The first part of the question for an IELTS discussion essay will be a statement containing two opposing views.

You will then be asked to discuss both sides of the argument and give your own opinion. Here is some typical wording that might be used:

• Discuss both views and give your opinion. 
• Discuss both these views and then give your own opinion. 
• Discuss both sides of this argument and give your own opinion.

Here's a question from a past test paper.

Some people think that zoos are cruel and should be closed down. Others, however, believe that zoos can be useful in protecting wild animals.

Discuss both views and give your opinion.

Give reasons for your answer and include any relevant examples from your own knowledge or experience.

Write at least 250 words.

I’ll be using this question to guide you through the process of planning and writing an IELTS discussion essay.

The key to identifying this type of question is the fact that you are required to discuss BOTH views. This is different to opinion questions where you must decide between two opposing views and make an argument to support your own opinion.

Opinion essays , also known as ‘agree or disagree’ essays, a generally worded in one of these ways:

What is your opinion? / Do you agree or disagree? / To what extent do you agree or disagree?

The other essay type that students mistake for discussion essays is advantages and disadvantages essays . With these, the statement will contain just one view and the question will typically be written as shown in this sample question.

School children are using computers in school more than ever.

Discuss the advantages and disadvantages of this and give your own opinion.

The consequence of incorrectly identifying the question type is that you will use the wrong structure for your essay. This is a major reason why people make the mistakes we’ll now look at.

3 Common Mistakes

These three errors are common in IELTS discussion essays.

• Not stating your opinion.
• Not giving arguments for both views.
• Not developing both sides of the argument equally.

The most common mistake that students make is not giving their opinion. The question will clearly state that you must choose one side of the argument to agree with. If you fail to do this, you will get a low score for task achievement.

It doesn’t matter which side of the argument you take or even, that you actually agree with it.

However, you must give equal attention to both sides. A common error is to provide a stronger argument for the view you favour. This leads to an unbalanced essay and a low score for task achievement. 

Essay Structure

Now let’s look at a simple structure you can use to write IELTS discussion essays. It’s not the only possible structure but it’s the one I recommend because it’s easy to learn and will enable you to quickly plan and write a high-level essay.

1)  Introduction

• Paraphrase the question
• State two supporting reasons
• Give your opinion

  2)  Main body paragraph 1

• Topic sentence – outline the view you don’t agree with
• Explanation – explain why this view is held by some people
• Example – give an example

 3 )  Main body paragraph 2

• Topic sentence – outline the view you do agree with

  4)  Conclusion

• Summarise the key points and state your opinion

This structure will give us a well-balanced essay with 4 paragraphs.

We now need some ideas to add into the structure and we’ll have everything we need for our essay.

How To Plan IELTS Discussion Essays

# 1  analyse the question.

This is an essential step in the planning process and will ensure that you answer the question fully. It’s quick and easy to do. You just need to identify 3 different types of words:

1. Topic words

2.  Other keywords

3.  Instruction words

We’ve already considered the instruction words (the actual question) so we’ll focus on the first two.

Topics words are the ones that identify the general subject of the question.

Some people think that zoos  are cruel and should be closed down. Others, however, believe that  zoos  can be useful in protecting wild animals.

So, this question is about ‘ zoos ’.

Many people do this first step of the process and then write about the topic in general. This is a serious mistake and leads to low marks for task achievement.

What we need to do now that we know the general topic, is to understand exactly what aspect of zoos we're being asked to write about.

The other keywords in the question tell you the specific topic you must write about. They define the opinions stated in the statement.

Some people think tha t zoos are cruel and should be closed down . Others, however, believe that zoos c an be useful in protecting wild animals .

By highlighting these words, it’s easy to see that you are being asked to write about the opposing views that zoos are cruel and should be closed down and that zoos can be useful in protecting wild animals. Your essay must only include ideas relevant to these ideas.

# 2  Decide on your opinion

As already mentioned, it doesn’t matter if you genuinely agree with the view you take in your essay or not. IELTS discussion essays are about your ability to write a well-structured essay in the English language and you will not be assessed on any opinion you might hold.

So, choose one view and make sure that your opinion is clear throughout the essay.

For this model essay, I’m going to agree with the statement that zoos are cruel and should be closed down.

# 3  Generate ideas

The next task is to generate some ideas to write about.

There are several different ways to think up ideas. I cover them fully on the  IELTS Essay Planning  page.

We’re going to use the ‘friends technique’. This is my preferred method as it allows you to take a step back from the stress of the exam situation and think more calmly.

Here’s how it works. Imagine you are chatting with a friend and they ask you the question in a casual conversation. What answers would you give them off the top of your head? Plan your essay around these ideas.

Doing this will help you to come up with simple answers in everyday language rather than straining your brain to think of amazing ideas using high level-language, which isn’t necessary.

You might want to try this yourself before reading on for my ideas.

Here are my ideas:

Cruel  – closed down:

• Cramped cages – animals distressed
• Unnatural environments
• Most animals not endangered
• Animals become a public spectacle for entertainment

Useful – protect wild animals:

• Research work to learn more about wild animals
• Breeding programmes for endangered species
• Some species saved from extinction
• Seeing wild animals close up inspires people to want to help protect them

I’ve got more ideas here than I need so I’m going to pick two to develop in the essay – one for each of the main body paragraphs.

Idea 1  –  Cramped cages & unnatural environments, animals distressed.

Idea 2  –  Breeding programmes for endangered species, some species saved from extinction.

We’re almost ready to start writing our IELTS discussion essay but first, we have one other small task to do.

# 4  Vocabulary

In an IELTS essay, it’s important to be able to say the same things in different ways, either by paraphrasing and/or using synonyms. During the planning stage, quickly jot down a few synonyms of key words you could use to save you having to stop and think of the right language while you’re writing.

For example:

zoos  – animals in captivity, collections of wild animals, menagerie, wildlife park

cruel  – to cause suffering, inhumane

protect  – safeguard, preserve

animals  – creatures, species

With that done, we can focus on the first paragraph of the essay – the introduction.

How To Write an Introduction

Good introductions to IELTS discussion essays have a simple 3 part structure:

1)  Paraphrase the question

2)  State two supporting reasons (outline statement)

3)  Give your opinion (thesis statement)

• Have 2-3 sentences
• Be 40-60 words long
• Take 5 minutes to write

Start your introduction by paraphrasing the question.

Question:   Some people think that zoos are cruel and should be closed down. Others, however, believe that zoos can be useful in protecting wild animals.

There are various phrases you can use to do this. Here are three examples. They all say the same thing using different language.

• Some people argue that… while others say that…
• It is considered by some…. while there are others who think….
• It is often argued that... whilst others disagree and think...

Choose one and add the details in the question statement in a paraphrased form. I recommend putting the view you don’t agree with first.

Paraphrased question:  

Some people argue that zoos help to preserve wild creatures, while others say that they are inhumane and should be abolished.

Note my use of synonyms. You don’t have to replace every key word but do so where possible whilst ensuring that your language sounds natural. There aren’t any suitable synonyms of ‘zoo’ that I can think of, so I've repeated this word from the statement.

2)  Thesis and outline statements

Now we need to add an  outline statement  where you outline the two main points that you’ll cover in the rest of the essay (ideas 1 and 2 above) and a  thesis statement  where you state your opinion.

Outline & thesis statements:

While the development of breeding programmes contributes to the preservation of endangered species, I believe that the poor conditions that many animals held in captivity are kept in make the existence of zoos unacceptable. 

So, let’s bring the three elements of our introduction together.

     Introduction

This introduction achieves three important functions:

• It shows the examiner that you understand the question.
• It acts as a guide to the examiner as to what your essay is about.
• It also helps to keep you focused and on track as you write.

The two ideas in your introduction will become your two main body paragraphs.

Main body paragraph 1  – Breeding programmes for endangered species, some species saved from extinction.

Main body paragraph 2  – Cramped cages & unnatural environments, animals distressed.

How To Write Main Body Paragraphs

Main body paragraphs in IELTS discussion essays should contain 3 things:

It is easier to begin by discussing the opinion you don’t agree with and then present the reasons for the opposing view that you support. So, we’ll start with idea 1.

Main Body Paragraph 1

The  topic sentence  summarises the main idea of the paragraph. That’s all it needs to do so it doesn’t have to be complicated.

It plays an important role in ensuring that your ideas flow logically from one to another. It does this by acting as a signpost for what is to come next, that is, what the paragraph will be about.

If you maintain a clear development of ideas throughout your essay, you will get high marks for task achievement and cohesion and coherence.

We’ll now take the idea for our first main body paragraph and create our topic sentence.

Topic sentence:  

On the one hand, there are many projects in existence in zoological parks around the world where species facing extinction have been successfully bred in captivity and their numbers increased substantially.

Next, we must write an  explanation sentence that expands on the idea. This explains to the examiner what we mean or why this is the case.

Explanation sentence: 

This is important for ensuring the survival of animals under threat from poaching and the destruction of their natural environments.

Finally, we add an  example  to support our main point. If you can’t think of a real example, it’s fine to make one up, as long as it’s believable. The examiner isn’t going to check your facts.

Example sentence:

A good example of this is the golden lion tamarin from Brazil which nearly died out because of logging and mining activities which are destroying its habitat. Today, a third of wild golden lion tamarins were raised in captivity.

That’s the 3 parts of our first main body paragraph complete. Here’s the finished paragraph.

We now follow the same process for our second main body paragraph.

Main Body Paragraph 2

Main idea 2  – Cramped cages & unnatural environments, animals distressed.

First, we write the  topic sentence  to summarise the main idea. I started main body paragraph 1 with the phrase ‘On the one hand...’, so main body paragraph 2 will naturally begin, ‘On the other hand... .

These are great cohesive devices to use when making a direct contrast between two opposing views and they link the ideas together well. They can be used in most IELTS discussion essays and will help to earn you a good score for cohesion and coherence.

Topic sentence:

On the other hand, a significant percentage of zoos house their animals in cramped cages with very little space to move around or behave naturally.

Now for the  explanation sentence  where we expand on this idea.

Explanation sentence:

This can lead to them becoming distressed and depressed as well as suffering physically through lack of exercise.

Finally, an  example  to support this point.

A friend of mine recently visited a wildlife park while on holiday abroad and was very upset to see the lions pacing up and down in a narrow, bare pen and eagles in enclosures so small that they were unable to fly.

That’s the 3 parts of our second main body paragraph complete. Here’s the finished paragraph.

Now we need a conclusion and our IELTS discussion essay is done.

How To Write a Conclusion

Conclusions to IELTS discussion essays should do two things:

• Summarise the main points
• State your opinion

This can generally be done in a single sentence.

If you're below the minimum 250 words after you’ve written your conclusion, you can add a prediction or recommendation statement.

Our essay currently has 231 words so we’re on target and don’t need this extra sentence but you can learn more about how to write a prediction or recommendation statement for IELTS discussion essays on the Task 2 Conclusions page.

The conclusion is the easiest sentence in the essay to write but one of the most important.

A good conclusion will:

• Neatly end the essay
• Link all your ideas together
• Sum up your argument or opinion
• Answer the question

If you achieve this, you’ll improve your score for both task achievement and cohesion and coherence which together make up 50% of the overall marks. Without a conclusion, you’ll score below band 6 for task achievement.

You can start almost any final paragraph of an IELTS discussion essay with the words:

• In conclusion

        or

• To conclude

Now all you need to do is briefly summarise the main ideas into one sentence.

Here’s a top tip . Go back and read the introduction to the essay because this is also a summary of the essay. It outlines what you are going to write about.

To create a great conclusion, you simply have to paraphrase the introduction. Let’s give it a go.

Introduction:

Here is the same information formed into a conclusion:

That’s it. We’ve completed our essay. Here it is with the 4 paragraphs put together.

Finished IELTS discussion essay.

Go through this lesson as many times as you need to in order to fully understand it and put in lots of practice writing IELTS discussion essays from past exam questions. Practice is the only way to improve your skills.

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More help with ielts discussion essays & other task 2 essays.

IELTS Writing Task 2  – T he format, the 5 question types, the 5 step essay writing strategy & sample questions. All the key information you need to know.

The 5 Types of Task 2 Essay   – How to recognise the 5 different types of Task 2 essays. 15 sample questions to study and a simple planning structure for each essay type.

Understanding Task 2 Questions  – How to quickly and easily analyse and understand IELTS Writing Task 2 questions.

How To Plan a Task 2 Essay  – Discover why essay planning is essential & learn a simple 4 step strategy, the 4 part essay structure & 4 methods of generating ideas.

How To Write a Task 2 Introduction  – Find out why a good introduction is essential. Learn how to write one using a simple 3 part strategy & discover 4 common mistakes to avoid.

How To Write Task 2 Main Body Paragraphs  – Learn the simple 3 part structure for writing great main body paragraphs and also, 3 common mistakes to avoid. 

How To Write Task 2 Conclusions  – Learn the easy way to write the perfect conclusion for a Task 2 essay. Also discover 4 common mistakes to avoid.

Task 2 Marking Criteria  – Find out how to meet the marking criteria in Task 2. See examples of good and poor answers & learn some common mistakes to avoid.

The 5 Task 2 Essay Types:

Step-by-step instructions on how to plan & write high-level essays. Model answers & common mistakes to avoid.

   Opinion Essays

   Discussion Essays

  Problem Solution Essays

  Advantages & Disadvantages Essays

  Double Question Essays

Other Related Pages

IELTS Writing Test  – Understand the format & marking criteria, know what skills are assessed & learn the difference between the Academic & General writing tests.

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How to Answer a Discuss Essay

When an essay title includes the word ‘Discuss’, this means that you are being asked to debate the subject of the essay. In other words, you need to be able to demonstrate that you have understood and evaluated both sides of the topic, problem, or opposing views in a theoretical perspective. At the same time, you need to be able to show, through rational evaluation of the evidence why you favour a particular view.

From this definition, it is clear that a ‘discuss’ essay is looking for balance, not bias or persuasion. In other words, the essay is not starting from one perspective and aiming to confirm this. Rather the intent of a ‘discuss’ essay is to deliver a work that clearly separates facts and opinions. The skills required for this include paraphrasing, summation, and the clear evaluation of different viewpoints. Common titles for a discuss essay include the format “AI is killing natural innovation from engineers. Discuss”, “Highlight and examine the advantages and disadvantages of home schooling for toddlers”, “Examine the arguments for and against the widespread mandatory delivery of the Covid-19 vaccine”. All of these titles require a discuss essay to be produced.

• A discuss essay of the highest standard will be logical, flow well and make arguments and statements based on knowledge and evidence, covering all perspectives.
• You should include all the most important (key) factors or issues in a subject area, highlighting where there is debate over these, ensuring that both sides of the argument are presented.
• Make statements and deliberations that are based only on credible and viable research, that has been previously well presented.

Structure of a Discuss Essay

Introduction.

In all essays the best introductions are those which draw in the reader with a strong statement from the outset.  The remainder of the introduction should give a brief indication of the subject being covered, the key points that will be discussed, and if you wish, anticipated conclusions. You should also incorporate any acronyms, or industry specific terms that will be covered in the essay.

Main Body of the work

The main body (or the meat of the essay) should be divided into separate paragraphs that each cover one distinct point or statement.  A discuss essay requires presentation of evidence, so each paragraph should be focused on one point with both for and against perspectives, before a final summary point identifying one or the other as being justified.  In all cases, any points made should be backed up by evidence, correctly cited and referenced at the end of your work.

Important point: The evidence provided, and references cited should only come from valid, credible sources, preferably peer-reviewed articles, and fully referenced. It is vital to ensure that the views expressed are not opinions but have been delivered based on evidence of wider reading in the field.

To ensure a logical flow, you should raise the main or key points of an arguments first, and then move onto sub-arguments, ensuring that all the paragraphs are well linked to deliver a cohesive, essay that flows in a logical way.

A discuss essay conclusion should contain two elements.  Firstly, a summary of the core ideas, returning to the evidence presented and the points made, along with an indication of which you believe delivered the strongest arguments for or against the statement in the title.

Secondly, a discuss essay should give your opinion, which should be grounded in the presented evidence, to demonstrate your ability to draw a conclusion from the data considered.  In other words, following an internal debate with yourself, evaluating the information available, you should demonstrate that you have an informed opinion on the subject under discussion.

To help you in the construction of your discussion essay, we have put together a list of key words and phrases that can be used to ensure you deliver a first-class piece of work.

Key Discussion Essay Vocabulary

When presenting evidence:.

• It is suggested that…
• Evidence available indicates that….
• It has been indicated that…
• Aspects of the work suggest that…
• The evidence presented supports the view that…
• The evidence presented however overlooks…
• Closer examination suggests….

For summarising, the following phrases are useful:

• The most important

When introducing an opinion:

• There is no doubt that…
• A key argument in favour is that…
• I believe that…

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• Knowledge Base
• Research paper
• How to Write a Discussion Section | Tips & Examples

How to Write a Discussion Section | Tips & Examples

Published on August 21, 2022 by Shona McCombes . Revised on July 18, 2023.

The discussion section is where you delve into the meaning, importance, and relevance of your results .

It should focus on explaining and evaluating what you found, showing how it relates to your literature review and paper or dissertation topic , and making an argument in support of your overall conclusion. It should not be a second results section.

There are different ways to write this section, but you can focus your writing around these key elements:

• Summary : A brief recap of your key results
• Interpretations: What do your results mean?
• Implications: Why do your results matter?
• Limitations: What can’t your results tell us?
• Recommendations: Avenues for further studies or analyses

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Table of contents

What not to include in your discussion section, step 1: summarize your key findings, step 2: give your interpretations, step 3: discuss the implications, step 4: acknowledge the limitations, step 5: share your recommendations, discussion section example, other interesting articles, frequently asked questions about discussion sections.

There are a few common mistakes to avoid when writing the discussion section of your paper.

• Don’t introduce new results: You should only discuss the data that you have already reported in your results section .
• Don’t make inflated claims: Avoid overinterpretation and speculation that isn’t directly supported by your data.
• Don’t undermine your research: The discussion of limitations should aim to strengthen your credibility, not emphasize weaknesses or failures.

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Start this section by reiterating your research problem and concisely summarizing your major findings. To speed up the process you can use a summarizer to quickly get an overview of all important findings. Don’t just repeat all the data you have already reported—aim for a clear statement of the overall result that directly answers your main research question . This should be no more than one paragraph.

Many students struggle with the differences between a discussion section and a results section . The crux of the matter is that your results sections should present your results, and your discussion section should subjectively evaluate them. Try not to blend elements of these two sections, in order to keep your paper sharp.

• The results indicate that…
• The study demonstrates a correlation between…
• This analysis supports the theory that…
• The data suggest that…

The meaning of your results may seem obvious to you, but it’s important to spell out their significance for your reader, showing exactly how they answer your research question.

The form of your interpretations will depend on the type of research, but some typical approaches to interpreting the data include:

• Identifying correlations , patterns, and relationships among the data
• Discussing whether the results met your expectations or supported your hypotheses
• Contextualizing your findings within previous research and theory
• Explaining unexpected results and evaluating their significance
• Considering possible alternative explanations and making an argument for your position

You can organize your discussion around key themes, hypotheses, or research questions, following the same structure as your results section. Alternatively, you can also begin by highlighting the most significant or unexpected results.

• In line with the hypothesis…
• Contrary to the hypothesized association…
• The results contradict the claims of Smith (2022) that…
• The results might suggest that x . However, based on the findings of similar studies, a more plausible explanation is y .

As well as giving your own interpretations, make sure to relate your results back to the scholarly work that you surveyed in the literature review . The discussion should show how your findings fit with existing knowledge, what new insights they contribute, and what consequences they have for theory or practice.

Ask yourself these questions:

• Do your results support or challenge existing theories? If they support existing theories, what new information do they contribute? If they challenge existing theories, why do you think that is?
• Are there any practical implications?

Your overall aim is to show the reader exactly what your research has contributed, and why they should care.

• These results build on existing evidence of…
• The results do not fit with the theory that…
• The experiment provides a new insight into the relationship between…
• These results should be taken into account when considering how to…
• The data contribute a clearer understanding of…
• While previous research has focused on  x , these results demonstrate that y .

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Even the best research has its limitations. Acknowledging these is important to demonstrate your credibility. Limitations aren’t about listing your errors, but about providing an accurate picture of what can and cannot be concluded from your study.

Limitations might be due to your overall research design, specific methodological choices , or unanticipated obstacles that emerged during your research process.

Here are a few common possibilities:

• If your sample size was small or limited to a specific group of people, explain how generalizability is limited.
• If you encountered problems when gathering or analyzing data, explain how these influenced the results.
• If there are potential confounding variables that you were unable to control, acknowledge the effect these may have had.

After noting the limitations, you can reiterate why the results are nonetheless valid for the purpose of answering your research question.

• The generalizability of the results is limited by…
• The reliability of these data is impacted by…
• Due to the lack of data on x , the results cannot confirm…
• The methodological choices were constrained by…
• It is beyond the scope of this study to…

Based on the discussion of your results, you can make recommendations for practical implementation or further research. Sometimes, the recommendations are saved for the conclusion .

Suggestions for further research can lead directly from the limitations. Don’t just state that more studies should be done—give concrete ideas for how future work can build on areas that your own research was unable to address.

• Further research is needed to establish…
• Future studies should take into account…
• Avenues for future research include…

If you want to know more about AI for academic writing, AI tools, or research bias, make sure to check out some of our other articles with explanations and examples or go directly to our tools!

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In the discussion , you explore the meaning and relevance of your research results , explaining how they fit with existing research and theory. Discuss:

• Your  interpretations : what do the results tell us?
• The  implications : why do the results matter?
• The  limitation s : what can’t the results tell us?

The results chapter or section simply and objectively reports what you found, without speculating on why you found these results. The discussion interprets the meaning of the results, puts them in context, and explains why they matter.

In qualitative research , results and discussion are sometimes combined. But in quantitative research , it’s considered important to separate the objective results from your interpretation of them.

In a thesis or dissertation, the discussion is an in-depth exploration of the results, going into detail about the meaning of your findings and citing relevant sources to put them in context.

The conclusion is more shorter and more general: it concisely answers your main research question and makes recommendations based on your overall findings.

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McCombes, S. (2023, July 18). How to Write a Discussion Section | Tips & Examples. Scribbr. Retrieved September 3, 2024, from https://www.scribbr.com/dissertation/discussion/

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IELTS Discuss Both Views Essay Structure + Sample Answers

The next big thing after learning about IELTS discuss both views essays is –  How do you structure them?

Please be aware though, the perfect structure alone will not make you a band 7+ achiever. Your vocabulary and English proficiency still plays a key role in IELTS writing task – 2.

But the good news is… Here we’ve outlined an easily comprehensible  step-by-step format  to logically present a discussion essay and give your opinion effectively.

This post will clear your doubts over:

• Essay Structure
• Sample Question(s)
• Task Explanation

Sample Answer

Discuss both views – essay structure.

There are hundreds of ways to structure a Discuss both views essay in the writing part . However, we’ll use this 4-paragraph foolproof band 7+ structure:

INTRODUCTION

• Paraphrase the question statement or use a general statement relevant to the topic.
• State both viewpoints
• Write your opinion statement (only if specified in the statement).
• Write an outline sentence

BODY PARAGRAPH 1

• State first viewpoint
• Explain the viewpoint
• Provide a logical example

BODY PARAGRAPH 2

• State second viewpoint
• Write concluding remarks and your opinion
• State which viewpoint is more significant

RELATED: IELTS Writing Task-1 Formal Letters With Sample Answers

Sample Questions

Now that you’ve understood the discussion essay structure, let’s look at some recently asked topics to give you an idea of how the ‘discuss both views and give your opinion’ essay looks like.

Some people believe that children should spend all of their leisure time with their families. Others believe that this is not required and a negative development. Discuss both viewpoints and give your opinion. Support your answer with the help of relevant examples.

Explanation of the Task

This is Opinion>Discussion type essay. Hence, You should introduce the topic, provide relevant ideas explaining arguments on both sides of the discussion, and then write your opinion in the conclusion. Always remember that these Opinion>Discussion tasks might be expressed differently; look for keyword ‘discuss’ and its synonyms like ‘debate’, ‘consider’ and ‘review’.

Topic Vocabulary

• foster parents – people who officially take a child into their family for a period of time, without becoming the child’s legal parents. The child is referred to as their foster child.
• guardians – people who are legally appointed to protect child’s interests in the absence of parents.
• role models – people that children look up to as examples
• ground rules – basic rules governing the peoples’ behaviour
• conventions – traditions or social norms that most people follow
• codes of conduct – voluntary rules acceptable to people
• bullying – when children attack and intimidate other children
• truancy – when a pupil leaves school without permission
• delinquency – minor crime
• dual-income – a situation when both mother and father working
• child-minding – informal care for children (outside of schools)
• peers – people in the same age group or level
• behavioural patterns – ways of acting and doing things
• well brought-up – to grow, educate and behave in a socially acceptable manner.

We hope that understanding this ‘Discuss both views essay structure’ will help you organize your writing task – 2 better and ultimately fetch you a high band score. And, don’t forget to download the IDP IELTS Writing answer sheets !

2 thoughts on “IELTS Discuss Both Views Essay Structure + Sample Answers”

Very good guidance. Could include one more sample answer.

Thanks! Yeah…sure. More stuff lined up 🙂

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The Structure of an Essay

Sep 25, 2014

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Lesson 9. The Structure of an Essay. What is an essay. An essay is a group of paragraphs written about a single topic and a central main idea. It must have at least three paragraphs, but a five-paragraph essay is a common assignment for academic writing. Structure sample.

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Lesson 9 The Structure of an Essay

What is an essay An essay is a group of paragraphs written about a single topic and a central main idea. It must have at least three paragraphs, but a five-paragraph essay is a common assignment for academic writing.

Structure sample

How to format an essay 1- Use double spacing (leave a blank line between each line of writing). 2- Leave 2.5 centimeters (1 inch) of space on the sides, and the top and bottom of the page. This space is called the margin. 3- If you type your essay, start the first line of each paragraph with five spaces ( one tab). This is called indenting. If you write by hand, indent about 2 centimeters. 4- Put the title of your essay at the top of the first page in the center.

Thesis statement What is a thesis statement? The thesis statement is the sentence that tells the main idea of the whole essay. It can be compared to a topic sentence, which gives the main idea of a paragraph. It usually comes at or near the end of the introductory paragraph.

Writing a strong thesis statement • A thesis statement gives the author’s opinion or states an important idea about the topic. It should give an idea that can be discussed and explained with supporting ideas. • Examples of strong thesis: • The qualifications for entering a university in my country are unreasonable. • When studying a second language 1

2 A thesis statement should not be a sentence that only gives a fact about the topic. Example of not strong thesis statement: In the Northern Hemisphere, the summer months are warmer than the winter months. The cause: it cannot be discussed or argued about.

3 A thesis statement shouldn’t state two sides of an argument equally. Example of not strong thesis statement: There are advantages and disadvantages to using nuclear power. This could be a topic sentence, but not a thesis statement . It could be revised like this: Although there are some advantages, using nuclear power has many disadvantages and should not be a part of our country’s energy plan.

How to connect the thesis statement and the essay? • The body paragraphs of an essay should always explain the thesis statement. • Each body paragraph should discuss one part of the thesis. • Example: • To create a successful advertisement, it is necessary for advertisers to answer three questions: What are we selling?, Who are we selling it to?, and How can we make people want to buy it?

1- What are we selling? The first step in creating a successful advertisement is to completely understand the product that is being sold and how it can be used. 2- Who are we selling it to? A second important part of creating an advertisement is deciding who is expected to buy the product. 3- How can we make people want to buy it? Finally, a way must be found to create an ad that will make people want to buy the product.

How to develop a thesis statement One way to develop a thesis statement for an essay is to write opinions you have about the topic. Begin, I think that … and the remaining words make a possible thesis statement. Example : Topic : diet / food I think that a vegetarian diet is one of the best ways to live a healthy life. I think that governments should restrict the use of chemicals in agriculture and food production.

Outlining Essay

What is an outline? • An outline is a list of the information you will put in your essay. • An outline: • Begins with the essay’s thesis statement. • Shows the organization of the essay. • Tells what ideas you will discuss and shows which ideas will come first, second, and so on. • Ends with the essay’s conclusion.

Writing an outline before you write an essay will help you on: • Showing you what to write before you actually begin writing. • making your essay well organized and clearly focused. • Keeping you from forgetting any important points.

How to write an outline? • Introduction • First main idea • A. first supporting point • 1- first detail • 2- second detail • B. second supporting point • 1- first detail • 2- second detail • III. Second main idea • A. first supporting point • 1- first detail • 2- second detail • B. second supporting point • 1- first detail • 2- second detail • Third main idea • A. first supporting point • 1- first detail • 2- second detail • B. second supporting point • 1- first detail • 2- second detail • V. Conclusion

Evaluating an outline

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25+ Informative Speech Topics To Engage Your Audience

• The Speaker Lab
• September 1, 2024

Table of Contents

A well-chosen topic is key. Not only does it hook your audience from the start, but it also ensures they’ll remember what you said long after. With so many possibilities, however, where do you even begin? Picking a speech topic can be difficult, but if you’re looking for informative speech topics , look no further. We’ve compiled a list of informative speech topics spanning a wide range of categories, from technology and social media to psychology and mental health. Each one has been chosen carefully so that your audience will learn loads while staying entertained. Whether you’re passionate about green living or sports, there’s a topic out there that’ll catch your attention and spark conversations.

What is an Informative Speech?

The main goal of an informative speech is to educate your audience about a specific subject. Accordingly, you want to present the information in a way that’s easy to understand and remember. Depending on your topic and goal, you can choose to speak on objects, processes, events, or concepts. Whatever type of informative speech you choose, just make sure it aligns with your audience’s interests and needs.

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Key Elements of an Informative Speech

To deliver an effective informative speech, there are a few key elements to keep in mind:

• Choose a clear, specific topic
• Conduct thorough research using credible sources
• Organize your speech in a logical, easy-to-follow structure
• Use engaging language and delivery techniques
• Conclude with a strong summary of your main points

By incorporating these elements into your speech writing process, you’ll be well on your way to delivering an informative and memorable speech.

How to Choose an Informative Speech Topic

Now that you know the basics of informative speeches, it’s time to choose your topic. But with so many options out there, where do you even begin? Don’t stress—we’ve got some tips to help you narrow down your choices and find the perfect informative speech topic.

Brainstorming Ideas

The first step in choosing a topic is to brainstorm potential ideas. Think about your interests, hobbies, and areas of expertise. What topics do you find fascinating? What do you want to learn more about? Jot down any and all ideas that come to mind, no matter how silly or far-fetched they may seem. After all, you never know what might spark inspiration for a great speech topic.

Narrowing Down Your Options

Once you have a list of potential topics, it’s time to start narrowing them down. Consider factors like the length of your speech, your audience’s interests and background knowledge, and the amount of research required for each topic.

Try to choose a topic that’s specific enough to cover in depth, but not so narrow that you’ll struggle to find enough information. And don’t be afraid to think outside the box—sometimes the most unique and creative informative speech topics are the most engaging.

Considering Your Audience

Your audience should always be at the forefront of your mind when choosing a speech topic. What do they want to learn about? What will capture their attention and keep them engaged? Consider factors like age, background, and interests when selecting your topic. You want to choose something that will resonate with your audience and leave them feeling informed and inspired.

Researching Your Topic

Once you’ve settled on a topic, it’s time to start researching. Look for credible sources like academic journals, reputable news outlets, and expert interviews to gather information and statistics. As you research, take notes and organize your findings into an outline. This will help you structure your speech and ensure you cover all the key points. Remember, the more knowledgeable you are about your topic, the more confident and engaging you’ll be when delivering your speech. So don’t skimp on the research phase.

Informative Speech Topics About Education

Education is a topic that affects us all, making it a great choice for an informative speech. Whether you’re passionate about bilingual education, curious about the pros and cons of online classes, or interested in the importance of physical education, there are plenty of angles to explore.

Some potential education-related informative speech topics include:

• The history of education in America
• The benefits and challenges of homeschooling
• The role of technology in modern education
• The importance of early childhood education
• The debate over standardized testing in schools

No matter which topic you choose, make sure to back up your points with research and statistics. And don’t be afraid to share your own experiences and opinions. After all, an informative speech is a great opportunity to educate and inspire your audience.

Psychology and Mental Health Informative Speech Topics

When it comes to informative speech topics about psychology and mental health, there’s no shortage of fascinating subjects to explore. From the inner workings of the human mind to the impact of mental well-being on our daily lives, this field offers a wealth of insights and discoveries. For instance, did you know that regular exercise can have a profound effect on our psychological well-being ? Studies have shown that physical activity can help reduce symptoms of depression, anxiety, and stress, while also boosting self-esteem and cognitive function. If topics like these interest you, then you may consider giving an informative speech on psychology and mental health.

The Mind-Body Connection

The mind-body connection is another topic that’s ripe for exploration in an informative speech. Our thoughts, emotions, and beliefs can have a powerful impact on our physical health, and vice versa. For example, chronic stress has been linked to a range of health problems, from heart disease to digestive issues. Meanwhile, embracing activities such as mindfulness or meditating brings with it perks aplenty. Bettering our brains alongside our bodies is only the start.

Of course, no discussion of psychology would be complete without delving into the complexities of human behavior. When you look at the way we build friendships or decide what’s next, there’s always something new and exciting to talk about. Wondering what to discuss? We’ve got a handful of killer suggestions ready for your upcoming presentation.

• The psychology of persuasion
• The impact of birth order on personality
• The science of habit formation
• The role of empathy in social interactions

Informative Speech Topics on Social Issues and Human Rights

Social issues and human rights are another rich source of informative speech topics. Not only are they relevant, but these topics are also great at keeping your audience hooked.

One topic that’s been in the spotlight in recent years is the impact of social media on our lives. While platforms like Facebook and Twitter have undoubtedly brought people together in new ways, they’ve also raised concerns about privacy, addiction, and the spread of misinformation. An informative speech on this topic might explore the pros and cons of social media use, as well as strategies for using these platforms in a healthy and responsible way.

Another pressing social issue is the ongoing fight for human rights around the world. Countries around the world have countless stories of courage and resilience just waiting to be told. So if you’re wondering what to discuss, take a look at these suggestions.

• The history of the civil rights movement
• The impact of gender discrimination on women’s lives
• The challenges faced by refugees and asylum seekers
• The role of activism in promoting social change

Technology and Social Media Informative Speech Topics

Technology and social media are transforming the way we live, work, and communicate. As a result, these topics offer endless possibilities for informative speeches that educate and inspire.

One recent technological development has been the rise of artificial intelligence (AI). From self-driving cars to personalized medicine, AI is poised to revolutionize nearly every aspect of our lives. If you chose to do an informative speech on AI, you could weigh the good against the bad—what amazing things AI can do for us and where it might trip us up.

Diving into another area, let’s talk about social media. In addition to the impact of social media on our personal lives, there’s also the question of how these platforms are shaping our political discourse and our society as a whole. Wondering what to discuss? We’ve got a handful of killer suggestions ready for your upcoming presentation.

• The role of social media in political campaigns
• The impact of online echo chambers on public opinion
• The ethics of social media data collection and use
• The potential for social media to promote social change

Environmental and Sustainability Informative Speech Topics

Environmental issues and sustainability are some of the most pressing challenges facing our world today. From climate change to plastic pollution, you’re never out of options for stirring speeches.

Climate change is, of course, a particularly urgent environmental topic. The scientific consensus is clear: By living the way we currently do, we’re pushing our planet’s temperature higher alarmingly quick, putting everything and everyone at risk. An informative speech on this topic might explore the causes and effects of climate change, as well as the steps we can take to mitigate its impact.

Other potential informative speech topics related to the environment and sustainability might include:

• The benefits of renewable energy sources like solar and wind power
• The impact of deforestation on biodiversity and climate change
• The problem of plastic pollution in our oceans and waterways
• The role of sustainable agriculture in feeding a growing population

No matter which topic you choose, an informative speech on psychology, social issues, technology, or the environment has the power to educate, inspire, and motivate your audience to take action. Dive into topics deeply and share what you find to spark change one reader at a time.

Unique and Creative Informative Speech Topics

Looking for a speech topic that’s a little out of the ordinary? Something that will really make your audience sit up and take notice? If so, you’ve come to the right place. Choosing a unique or creative topic is a surefire way to make your informative speech memorable. It’s a chance to showcase your personality and interests while still delivering valuable information. In addition, it’s just more fun to research and write about something a little offbeat. Below are a few creative ideas to get you going.

• Unusual holidays and festivals around the world
• The history and science behind a common food item (like chocolate or coffee)
• How a popular board game or toy is made
• The life and accomplishments of a little-known historical figure
• The psychology of optical illusions and how they trick our brains

The key is to find a topic that piques your curiosity and hasn’t been done to death. Dig deep into your hobbies, passions, and areas of expertise. Chances are, there’s a fascinating informative speech topic hiding in there somewhere. In fact, some of the best informative speeches are the ones that take a familiar topic and approach it from a completely new angle. For example, instead of giving a generic speech about the importance of recycling, you could focus on the surprising ways recycled materials are used in fashion or art.

The possibilities are endless. With a little creativity and research, you can craft a truly unique informative speech that will leave a lasting impression on your audience.

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Tips for Delivering an Engaging Informative Speech

You’ve chosen the perfect informative speech topic, done your research, and written a great speech outline . Now comes the hard part: actually delivering the speech in front of an audience. Don’t worry, though, because we have your back.

Giving a great speech is all about preparation and practice. The more comfortable you are with your material, the more confident and engaging you’ll be on stage. Here are a few tips to help you deliver an informative speech that will keep your audience hooked from beginning to end.

Organizing Your Speech

The structure of your speech is just as important as the content itself. A well-organized informative speech has a clear beginning, middle, and end. Start with an attention-grabbing introduction that previews your main points. Use the body of your speech to dive deeper into each point, using examples and stories to illustrate your ideas. Finally, wrap things up with a memorable conclusion that reinforces your key takeaways.

Using Visual Aids

Visual aids like slides, charts, or props can be a great way to enhance your informative speech and make complex topics more accessible. Just be sure to use them sparingly and strategically. Too many visuals can be distracting, so choose ones that really drive home your main points. And always have a backup plan in case of technical difficulties.

Connecting with Your Audience

At the end of the day, the goal of any informative speech is to educate and engage your audience. To do that, you need to find ways to make your topic relatable and relevant to their lives. Use examples and anecdotes that resonate with their experiences. Make eye contact, smile, and use gestures to convey your enthusiasm for the subject. And don’t be afraid to inject a little humor or personality into your delivery.

Practicing and Refining Your Delivery

The old saying “practice makes perfect” definitely applies to public speaking . The more you rehearse your informative speech, the more natural and polished your delivery will become. Practice in front of a mirror, record yourself on video, or grab a friend to be your audience. Pay attention to your pacing, clarity, and body language . And don’t forget to time yourself to make sure you’re staying within the allotted time limit.

Remember, delivering a great informative speech is a skill that anyone can learn with a little practice and preparation. So take a deep breath, trust in your abilities, and go out there and crush it.

FAQs About Informative Speech Topics

What are the 5 useful topics of an informative speech.

Consider technology trends, mental health awareness, climate change impacts, historical events analysis, and modern educational methods for engaging speeches.

What is a good informative speech?

A good one dives deep into facts and insights without trying to sway opinions. It’s clear, precise, and keeps listeners hooked.

What is an appropriate topic for an informative speech about a concept?

The evolution of artificial intelligence presents a rich ground to explore concepts ranging from ethics to its societal impact.

Which topic is best for speech?

Pick something you’re passionate about. If it sparks your interest, chances are high it’ll engage your audience too.

To truly master an informative speech, you have to get excited about your chosen subject. Spend ample time researching every nook and cranny then wrap it up by enthralling everyone through compelling narratives peppered with interesting tidbits. Use the informative speech topics we’ve shared with you and you’re all set to create a presentation that not only shares knowledge but also keeps your audience hooked and leaves them thinking.

So, whether you’re a student, professional speaker, or simply looking to enhance your public speaking skills, embrace the power of informative speeches. Choose a topic that ignites your curiosity, and watch as your words inspire and educate others.

• Last Updated: August 28, 2024

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The worldwide catastrophe of rising seas especially imperils Pacific paradises, Guterres says

FILE - Tourists watch the sun set along a popular beach in Tamuning, Guam, May 6, 2019. (AP Photo/David Goldman, File)

United Nations Secretary-General Antonio Guterres speaks at the opening of the annual Pacific Islands Forum leaders meeting in Nuku’alofa, Tonga, Monday, Aug. 26, 2024. (AP Photo/Charlotte Graham-McLay)

High school students march for climate justice as Pacific leaders meet in Nuku’alofa, Tonga, Tuesday, Aug. 27, 2024. (AP Photo/Charlotte Graham-McLay)

Vanuatu Prime Minister Charlot Salwai, from left, Niue Prime Minister Dalton Tagelagi and New Zealand Foreign Minister Winston Peters attend the opening of the annual Pacific Islands Forum leaders meeting in Nuku’alofa, Tonga, Monday, Aug. 26, 2024. (AP Photo/Charlotte Graham-McLay)

FILE - A section of land between trees is washed away due to rising seas on Nov. 6, 2015, in Majuro Atoll, Marshall Islands. (AP Photo/Rob Griffith, File)

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NUKU’ALOFA, Tonga (AP) — Highlighting seas that are rising at an accelerating rate, especially in the far more vulnerable Pacific island nations, U.N. Secretary-General Antonio Guterres issued yet another climate SOS to the world. This time he said those initials stand for “save our seas.”

The United Nations and the World Meteorological Organization Monday issued reports on worsening sea level rise, turbocharged by a warming Earth and melting ice sheets and glaciers. They highlight how the Southwestern Pacific is not only hurt by the rising oceans, but by other climate change effects of ocean acidification and marine heat waves.

Guterres toured Samoa and Tonga and made his climate plea from Tonga’s capital on Tuesday at a meeting of the Pacific Islands Forum, whose member countries are among those most imperiled by climate change. Next month the United Nations General Assembly holds a special session to discuss rising seas .

U.N. Secretary-General Antonio Guterres issued yet another climate SOS to the world, highlighting seas that are rising at an accelerating rate, especially in the far more vulnerable Pacific island nations.

“This is a crazy situation,” Guterres said. “Rising seas are a crisis entirely of humanity’s making. A crisis that will soon swell to an almost unimaginable scale, with no lifeboat to take us back to safety.”

“A worldwide catastrophe is putting this Pacific paradise in peril,” he said. “The ocean is overflowing.”

A report that Guterres’ office commissioned found that sea level lapping against Tonga’s capital Nuku’alofa had risen 21 centimeters (8.3 inches) between 1990 and 2020, twice the global average of 10 centimeters (3.9 inches). Apia, Samoa, has seen 31 centimeters (1 foot) of rising seas, while Suva-B, Fiji has had 29 centimeters (11.4 inches).

“This puts Pacific Island nations in grave danger,” Guterres said. About 90% of the region’s people live within 5 kilometers (3 miles) of the rising oceans, he said.

Since 1980, coastal flooding in Guam has jumped from twice a year to 22 times a year. It’s gone from five times a year to 43 times a year in the Cook Islands. In Pago Pago, American Samoa, coastal flooding went from zero to 102 times a year, according to the WMO State of the Climate in the South-West Pacific 2023 report.

“Because of sea level rise, the ocean is transforming from being a lifelong friend into a growing threat,” Celeste Saulo, secretary-general of the World Meteorological Organization, told reporters in Nuku’alofa on Tuesday.

While the western edges of the Pacific are seeing sea level rise about twice the global average, the central Pacific is closer to the global average, the WMO said.

Sea levels are rising faster in the western tropical Pacific because of where the melting ice from western Antarctica heads, warmer waters and ocean currents, UN officials said.

Guterres said he can see changes since the last time he was in the region in May 2019.

While he met in Nuku’alofa on Tuesday with Pacific nations on the environment at their leaders’ annual summit, a hundred local high school students and activists from across the Pacific marched for climate justice a few blocks away.

One of the marchers was Itinterunga Rae of the Barnaban Human Rights Defenders Network, whose people were forced generations ago to relocate to Fiji from their Kiribati island home due to environmental degradation. Rae said abandoning Pacific islands should not be seen as a solution to rising seas.

“We promote climate mobility as a solution to be safe from your island that’s been destroyed by climate change, but it’s not the safest option,” he said. Barnabans have been cut off from the source of their culture and heritage, he said.

“The alarm is justified,” said S. Jeffress Williams, a retired U.S. Geological Survey sea level scientist. He said it’s especially bad for the Pacific islands because most of the islands are at low elevations, so people are more likely to get hurt. Three outside experts said the sea level reports accurately reflect what’s happening.

The Pacific is getting hit hard despite only producing 0.2% of heat-trapping gases causing climate change and expanding oceans, the UN said. The largest chunk of the sea rise is from melting ice sheets in Antarctica and Greenland. Melting land glaciers add to that, and warmer water also expands based on the laws of physics.

Antarctic and Greenland “melting has greatly accelerated over the past three to four decades due to high rate of warming at the poles,” Williams, who was not part of the reports, said in an email.

About 90% of the heat trapped by greenhouse gases goes into the oceans, the UN said.

Globally, sea level rise has been accelerating, the UN report said, echoing peer-reviewed studies . The rate is now the fastest it has been in 3,000 years, Guterres said.

Between 1901 and 1971, the global average sea rise was 1.3 centimeters a decade, according to the UN report. Between 1971 and 2006 it jumped to 1.9 centimeters per decade, then between 2006 and 2018 it was up to 3.7 centimeters a decade. The last decade, seas have risen 4.8 centimeters (1.9 inches).

The UN report also highlighted cities in the richest 20 nations, which account for 80% of the heat-trapping gases, where rising seas are lapping at large population centers. Those cities where sea level rise in the past 30 years has been at least 50% higher than the global average include Shanghai; Perth, Australia; London; Atlantic City, New Jersey; Boston; Miami; and New Orleans.

New Orleans topped the list with 10.2 inches (26 centimeters) of sea level rise between 1990 and 2020. UN officials highlighted the flooding in New York City during 2012’s Superstorm Sandy as worsened by rising seas. A 2021 study said climate-driven sea level rise added $8 billion to the storm’s costs.

Guterres is amping up his rhetoric on what he calls “climate chaos” and urged richer nations to step up efforts to reduce carbon emissions, end fossil fuel use and help poorer nations. Yet countries’ energy plans show them producing double the amount of fossil fuels in 2030 than the amount that would limit warming to internationally agreed upon levels, a 2023 UN report found.

Guterres said he expects Pacific island nations to “speak loud and clear” in the next General Assembly, and because they contribute so little to climate change, “they have a moral authority to ask those that are creating accelerating the sea level rise to reverse these trends.”

Borenstein reported from Kensington, Maryland.

Follow Seth Borenstein and Charlotte Graham-McLay on X at @borenbears and @CGrahamMcLay

Read more of AP’s climate coverage at http://www.apnews.com/climate-and-environment

The Associated Press’ climate and environmental coverage receives financial support from multiple private foundations. AP is solely responsible for all content. Find AP’s standards for working with philanthropies, a list of supporters and funded coverage areas at AP.org .

• Open access
• Published: 30 August 2024

BRD4: an effective target for organ fibrosis

• Qun Wei 1   na1 ,
• Cailing Gan 1   na1 ,
• Meng Sun 1 ,
• Yuting Xie 1 ,
• Hongyao Liu 1 ,
• Taixiong Xue 1 ,
• Conghui Deng 1 ,
• Chunheng Mo 2 &
• Tinghong Ye 1 , 3  

Biomarker Research volume  12 , Article number:  92 ( 2024 ) Cite this article

Metrics details

Fibrosis is an excessive wound-healing response induced by repeated or chronic external stimuli to tissues, significantly impacting quality of life and primarily contributing to organ failure. Organ fibrosis is reported to cause 45% of all-cause mortality worldwide. Despite extensive efforts to develop new antifibrotic drugs, drug discovery has not kept pace with the clinical demand. Currently, only pirfenidone and nintedanib are approved by the FDA to treat pulmonary fibrotic illness, whereas there are currently no available antifibrotic drugs for hepatic, cardiac or renal fibrosis. The development of fibrosis is closely related to epigenetic alterations. The field of epigenetics primarily studies biological processes, including chromatin modifications, epigenetic readers, DNA transcription and RNA translation. The bromodomain and extra-terminal structural domain (BET) family, a class of epigenetic readers, specifically recognizes acetylated histone lysine residues and promotes the formation of transcriptional complexes. Bromodomain-containing protein 4 (BRD4) is one of the most well-researched proteins in the BET family. BRD4 is implicated in the expression of genes related to inflammation and pro-fibrosis during fibrosis. Inhibition of BRD4 has shown promising anti-fibrotic effects in preclinical studies; however, no BRD4 inhibitor has been approved for clinical use. This review introduces the structure and function of BET proteins, the research progress on BRD4 in organ fibrosis, and the inhibitors of BRD4 utilized in fibrosis. We emphasize the feasibility of targeting BRD4 as an anti-fibrotic strategy and discuss the therapeutic potential and challenges associated with BRD4 inhibitors in treating fibrotic diseases.

Introduction

Fibrosis is an excessive wound-healing process induced by repeated or chronic tissue damage due to persistent external stimuli [ 1 , 2 , 3 , 4 ]. It can occur in a variety of solid organs or tissues and accounts for 45% of all-cause mortality worldwide [ 5 , 6 ]. Organ fibrosis, which affects the heart, liver, lungs, and kidneys, is a common complication of chronic diseases such as diabetes mellitus, hypertension, heart disease, and viral or non-viral hepatitis. These conditions can lead to further complications, such as liver cirrhosis, interstitial lung disease, diabetic nephropathy, and heart failure [ 7 ]. Currently, pirfenidone and nintedanib are the only drugs approved by the FDA to treat pulmonary fibrosis [ 8 , 9 ]. However, these drugs have no efficacy in reversing the pathological process of pulmonary fibrosis and have side effects [ 10 , 11 , 12 ]. Moreover, there are no clinically approved therapeutic agents for treating cardiac, hepatic, or renal fibrosis. Therefore, it is imperative to find efficient targets for organ fibrosis and to create pharmaceuticals that are therapeutically antifibrotic.

Given the enormous threat to human health posed by organ fibrosis, our focus is on the pathological mechanisms underlying its development. When body organs are exposed to external stimuli, damaged cells first undergo necrosis [ 13 ]. Damaged cells results in the secretion of inflammatory mediators and the recruitment of inflammatory cells, thus triggering inflammation [ 14 , 15 ]. Inflammatory cells secrete pro-inflammatory and pro-fibrotic chemokines or cytokines (e.g., transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), platelet-derived growth factor (PDGF), interleukin-6 (IL-6), interleukin-1β (IL-1β), and C–C motif chemokine ligand 2 (CCL2)) [ 16 ]. These factors induce the expression or silencing of fibrosis-related genes in cells surrounding damaged tissues (e.g., endothelial cells, epithelial cells, fibroblasts, hepatic stellate cells (HSCs), pericytes, etc.) [ 17 ], which causes precursor cells to transform into myofibroblasts [ 18 ]. Activated and proliferating myofibroblasts rapidly synthesize and secrete the extracellular matrix (ECM) [ 19 , 20 , 21 , 22 , 23 ]. After the completion of tissue repair, when the external stimulus is eradicated, the pro-fibrotic mechanism and anti-fibrotic mechanism in the tissue reach a balance [ 24 ]. The ECM is remodeled or degraded, and activated myofibroblasts are inactivated through apoptosis, senescence, dedifferentiation, and reprogramming [ 25 ]. Parenchymal tissues eventually achieve structural and functional repair, thus completing the normal wound healing process [ 3 ]. However, human fibrotic diseases often result from a variety of stimuli. Long-term chronic recurrent tissue injury leads to continuous activation of myofibroblasts and persistent ECM deposition [ 26 ]. This leads to gradual escape from the normal biological control of fibrotic repair mechanisms. Excessive ECM disrupts normal tissue structure and physiological function and ultimately leads to organ failure and related complications [ 27 , 28 , 29 , 30 ] [Fig.  1 ].

Schematic diagram of the mechanism of organ fibrosis. When tissues and organs such as the heart, liver, lung and kidney are subjected to sustained external injury, damaged parenchymal cells initiate injury-related molecular patterns, secrete inflammatory mediators, recruit inflammatory cells, and promote inflammation in damaged tissues. Quiescent fibroblasts in these organs are activated to become myofibroblasts in response to the body's repair response to damaged tissues, and epithelial-mesenchymal transition (EMT) and endothelial-mesenchymal transition (EndMT) further increase the number of myofibroblasts in damaged organs. Myofibroblasts continuously secrete extracellular matrix (ECM), such as α-smooth muscle actin (α-SMA), collagen I (COL I), and fibronectin (FN), which leads to the development of organ fibrosis [ 7 , 67 , 68 , 69 , 70 ]

The process of organ fibrosis involves external stimuli that induce the activation of fibroblasts and effector cells. This activation leads to changes in intracellular epigenetics and the expression of fibrotic genes, thereby activating fibrotic signaling pathways and altering the fibrotic phenotypes of cells, tissues, and organs [ 31 , 32 ]. Epigenetic alterations and the transcription of fibrotic genes are critical in this process [ 33 , 34 ]. Gene transcription is controlled by interactions between DNA, chromatin modifications, readers, and RNA polymerase II (RNA Pol II) [ 35 , 36 , 37 , 38 , 39 ]. Among chromatin modifications, histone acetylation can regulate chromatin function, thereby disrupting the highly helical structure between DNA and histones. This can modulate the accessibility of genes to the transcriptional machinery and promote the transcription of active genes [ 40 , 41 , 42 , 43 , 44 ]. Histone acetylation is tightly controlled by histone acetyltransferases (HAT) and histone deacetylases (HDAC). HATs include three families, GNAT, MYST, and CBP/P300, and can be considered transcriptional coactivators [ 45 , 46 , 47 , 48 , 49 , 50 ]. Histone acetylation marks can be specifically recognized by the epigenetic readout domains of BET families [ 51 , 52 , 53 ].

The BET family is a class of epigenetic readers, which are widely studied bromodomain (BRD) proteins whose members are mainly bromodomain-containing protein 2 (BRD2), bromodomain-containing protein 3 (BRD3), BRD4 and bromodomain testis-specific protein (BRDT) [ 54 ]. BET family proteins can specifically recognize and bind to acetylated lysine (KAc) residues on histones and nonhistone proteins [ 55 ]. This alters chromatin accessibility to transcription factors (TFs), inducing a shift to an active transcriptional state. Furthermore, coactivator proteins involved in transcription initiation and elongation are recruited to histone acetylation marker proteins to promote gene transcription [ 56 , 57 , 58 , 59 ]. BRD4 is one of the BET family's most thoroughly researched members. It can form transcription complexes in genomic regions with transcription elements such as TFs and transcription cofactor complex mediators [ 60 , 61 ]. In recent years, BRD4 and BRD4 inhibitors have been extensively studied in the contexts of cancer, inflammation, viral infections, organ fibrosis, etc. [ 61 , 62 , 63 , 64 , 65 , 66 ]. The development of BRD4 inhibitors has contributed to the understanding of the role of BRD4 in physiological and pathological processes. Owing to the role of BRD4 in bridging the gap between epigenetic alterations and gene expression, this review focuses on recent progress in understanding the role of BRD4 in organ fibrosis. We introduce the structure and biological functions of BRD4 and summarize BRD4 inhibitors that have been used in organ fibrosis. We further discuss the potential of BRD4 as an anti-fibrotic target, highlighting the therapeutic prospects of BRD4 inhibitors in treating organ fibrosis.

Structure and function of BET proteins

The four members of the BET family are BRDT, BRD2, BRD3 and BRD4. While BRDT is expressed only in the testis of the male germline, BRD2, BRD3, and BRD4 are universally expressed in all tissues. Two tandem bromodomains (BD1 and BD2) and an extra-terminal (ET) structural domain are present in all BET protein family members. Among them, the bromo-structural domain mainly consists of approximately 110 amino acids. It has four major α-helices (αZ, αA, αB, and αC) in its structure and is connected by two loops (ZA and BC), which link αZ, αA, and αB, αC, respectively [ 54 , 71 , 72 , 73 ]. These loops form a central hydrophobic pocket that binds specifically to acetylated lysine residues of histones or other proteins [ 71 , 74 , 75 , 76 ]. The acetylated lysine residues are recognized primarily by asparagine residues in the central hydrophobic pocket [ 77 , 78 ]. BD1 and BD2 of BRD4 exhibit different binding activities for different acetylated lysine residues [ 79 ]. BD1 mainly binds to histone acetylated lysine residues, whereas BD2 mainly binds to other nonhistone acetylated lysine residues [ 80 ], such as acetylated lysine residues of RelA and cycle T1 (Cyc T1) [ 81 , 82 ]. The ET structural domain consists of approximately 80 amino acids [ 72 ]. BET proteins mainly recruit TFs or other specific proteins through the ET structural domain to coregulate the transcription of target genes [ 83 , 84 ].

In addition, other structural domains have been identified in the BRD4 protein, such as the serine-rich N-terminal phosphorylation site (NPS), which is essential for the binding of BD2 to acetylated lysine residues. The base-interacting structural domain (BID) carries a positive charge and can form intramolecular contacts with the negatively charged phosphorylated NPS, thereby inhibiting the binding of BD2 to acetylated lysine residues [ 84 , 85 , 86 ]. BRD4 also contains a serine-rich C-terminal phosphorylation site (CPS) [ 87 , 88 ]. Furthermore, an additional C-terminal domain (CTD), also referred to as the positive transcription elongation factor b (P-TEFb) interaction domain (PID), is present in the long forms of BRD4 and BRDT and interacts with P-TEFb [ 89 , 90 ]. P-TEFb is a complex consisting mainly of cell cycle-dependent kinase 9 (CDK9) and Cyc T1 [ 84 , 91 ]. P-TEFb mostly resides in an inactive form bound to the HEXIM1 protein and the 7SK small nuclear ribonucleoprotein (SnRNP) when it is not bound to BRD4 [ 92 , 93 , 94 , 95 , 96 , 97 ]. P-TEFb binding to the CTD of BRD4 inhibits the binding of P-TEFb to HEXIM1 and converts P-TEFb to its active form [ 98 , 99 , 100 , 101 ]. Ser2 of the RNA Pol II C-terminal motif (CTM) can be phosphorylated by active P-TEFb [ 101 , 102 , 103 ], facilitating transcription elongation involving RNA pol II [ 89 , 104 , 105 , 106 , 107 ]. BRD4 also exhibits atypical histone acetyltransferase activity (BRD4-HAT), which acetylates lysine residue 122 on histone H3 (H3K122) [ 108 , 109 ]. Upon binding to the promoter of the target gene, BRD4 also acetylates lysine residues on neighboring histones, mediating nucleosome dissociation and promoting target gene accessibility for the transcriptional complex [ 108 ]. The short variant of BRD4 lacks both intrinsic HAT activity and CTD structural domains [Fig.  2 ]. In addition, BRD4 was identified as an atypical kinase capable of directly phosphorylating serine 2 (Ser2) of the CTM of RNA pol II which is involved in gene transcription [ 110 ].

Structures of four members of the human bromodomain and extra-terminal structural domain (BET) family of proteins. All BET proteins have two tandem bromodomains (BD1, BD2) and an extra-terminal structural domain (ET), and the ET structural domains are indicated in pink. There are additional C-terminal domains (CTD), also known as positive transcription elongation factor b (P-TEFb) interaction domain (PID), in the long variant of BRD4 and in the BRDT proteins; CTD structural domains are indicated in orange. The short variant of BRD4 does not have CTD structural domains or histone acetyltransferases (HAT) kinase activity. Additionally, other structural domains were identified in the BRD4 protein, including the N-segment phosphorylation site (NPS), indicated in purple, with an amino acid range of 472–500; the basic residue-enriched structural domain, also known as the basic interaction structural domain (BID), indicated in yellow, with an amino acid range of 524–579; and the C-terminal phosphorylation site (CPS), indicated in green, with an amino acid range of 697–720. Among them, the bromodomain (BD1, BD2) mainly binds to acetylated lysine residues on histones and nonhistone proteins; the ET structural domain mainly mediates interactions with proteins such as transcription factors (TFs); the CTD is mainly responsible for the recruitment of and interaction with P-TEFb; and the NPS is negatively charged, which promotes BD2 binding to acetylated lysine residues, BID is positively charged and can form intramolecular contacts with NPS and inhibit BD2 binding to acetylated lysine residues

BRD4 plays a crucial role in the NF-kB-mediated inflammatory gene expression system. NF-kB is a heterodimer consisting of P50 and RelA. Normally, NF-kB is present in the cytoplasm and is bound to the inhibitor IkBα [ 111 , 112 , 113 , 114 ]. External stimuli lead to the phosphorylation and subsequent degradation of IkBα by triggering the activation of IkB kinase [ 115 , 116 , 117 ]. This process releases NF-κB from the inactive complex, allowing it to translocate to the nucleus [ 118 ]. Once inside the nucleus, NF-kB binds to NF-kB sites at the promoter of the target gene [ 119 ]. The histone acetyltransferase P300/CBP acetylates lysine 310 on RelA, a modification crucial for gene activation [ 120 , 121 , 122 , 123 ]. Acetylated lysine residues on RelA are recognized and bound by BRD4, which then recruits P-TEFb [ 117 , 124 ]. P-TEFb phosphorylates the CTM of RNA Pol II via the kinase activity of CDK9 [ 124 , 125 ]. This promotes the transcription of inflammatory target genes associated with NF-kB [ 112 ]. Additionally, BRD4 promotes lysine 310 acetylation of RelA through its atypical acetyltransferase activity, which mediates inflammatory gene transcription [ 84 ][Fig.  3 ].

Schematic representation of the function of BRD4. In the presence of histone acetyltransferase (CBP/P300), lysine residues on histones are acetylated, and BRD4 binds to acetylated lysine residues and recruits transcription mediators (Mediator), TFs and P-TEFb. Then Ser2 of the RNA polymerase II (RNA Pol II) C-terminal motif (CTM) is phosphorylated via the cycle-dependent kinase 9 (CDK9) in P-TEFb, facilitating the transcription elongation of RNA Pol II. NF-kB consists of P50 and RelA dissociates from IkBα and translocates to the nucleus. Binds to the promoter of the target gene at the NF-kB site. In the presence of P300/CBP, the lysine at position 310 of RelA is acetylated. BRD4 binds to acetylated RelA and recruits P-TEFb. P-TEFb phosphorylates the CTM of RNA Pol II and promotes the transcription of NF-kB-related inflammatory genes

BRD4 in organ fibrosis

Brd4 in cardiac fibrosis.

Cardiac fibrosis is a prevalent pathophysiological process in a variety of cardiac diseases, including heart failure, myocardial infarction (MI), hypertensive heart disease, aortic stenosis, hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and diabetic cardiomyopathy [ 126 ]. Cardiac fibroblasts (CFs) are the primary effector cells of the heart that respond to various external stimuli leading to pathological damage [ 127 , 128 , 129 ]. In the process of myocardial injury caused by external stimuli such as myocardial hypoxia, pressure overload, volume overload [ 126 ], apoptosis and necrosis of cardiomyocytes, infiltration of inflammatory cells, and activation of CFs gradually occur in damaged foci of the heart, initiating the process of cardiac repair [ 130 ]. Sustained external stimulation leads to overactivation of CFs and excessive ECM deposition, inducing cardiac fibrosis. Multiple signaling pathways, including the TGF-β signaling pathway, the renin–angiotensin–aldosterone system [ 131 ], endothelin, etc., are involved in CFs activation as well as in the process of cardiac pathological remodeling. Cardiac fibrosis leads to cardiac tissue stiffness [ 132 ], ventricular diastolic-systolic dysfunction [ 133 ], and impaired electrical conduction, which can trigger cardiac dysfunction and heart failure [ 126 , 134 , 135 ].

Matthew S. Stratton et al. Demonstrated via RNA sequencing and mass spectrometry that BRD4 in CFs is significantly enriched in a subpopulation of promoters, active enhancers, or superenhancers associated with fibrosis in response to stimulation by external factors such as TGF-β and transverse aortic constriction (TAC). This in turn regulates CFs activation in vitro and in vivo. BRD4 function is partially regulated by p38 mitogen-activated protein kinase (MAPK) [ 136 ]. Fortunately, Matthew S. Stratton et al. reported that microRNA-9 is able to target the 3'UTR of the BRD4 transcript. MicroRNA-9 was able to suppress BRD4 expression in normal cardiomyocytes. Downregulation of microRNA-9 due to external stimuli leads to increased BRD4 expression and enrichment at distal superenhancers [ 137 ]. These findings suggest that BRD4 might mediate the progression of cardiac fibrosis. Given that BRD4 has an epigenetic reader function and transcriptional complex recruitment capacity. We found that BRD4 promotes the expression of cardiac pathology biomarkers by interacting with P-TEFb, facilitating transcription elongation and suspending RNA Pol II release. Importantly, BET inhibitors have been shown to significantly reduce RNA Pol II phosphorylation levels and attenuate its transcriptional elongation [ 138 , 139 ]. Thus, we believe that BRD4 inhibition could play a therapeutic role in cardiac fibrosis. Isoprenaline (ISO) stimulation promotes PARylation of the BRD4 CTD structural domain by poly (ADP-ribose) polymerase-1 (PARP1). This modification promotes BRD4 binding to the transcriptional start sites of hypertrophic genes, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), leading to increased RNA Pol II phosphorylation and hypertrophic gene transcriptional activation [ 140 ]. Dingyan Zhou et al. reported that ISO was able to induce the acetylation of H3K122 and the phosphorylation of RNA Pol II. Bellidifolin (BEL), the active xanthone component of gentian, inhibits the protein levels of BRD4 and NADPH oxidase 4 (NOX4), and reduces ISO-induced acetylation of H3K122 and phosphorylation of RNA Pol II. This led to a reduction in the expression of the cardiac hypertrophy marker proteins ANP and BNP in the mouse heart, which in turn ameliorated myocardial hypertrophy as well as cardiac fibrosis [ 141 ].

Numerous researchers have investigated the therapeutic benefits and mechanisms of action of BRD4 inhibitors in heart disease because BRD4 functions in controlling gene expression in heart disease. As described below, BRD4 inhibition has been shown to play a therapeutic role in cardiac fibrosis caused by various types of cardiac injury. First, Shuai Song et al. demonstrated that BRD4 is upregulated in TAC mouse cardiac endothelial cells and in TGF-β-treated mouse cardiac endothelial cells. BRD4 promotes the migration of human umbilical vein endothelial cells (HUVECs) and mouse aortic endothelial cells (MAECs) and induces endothelial-mesenchymal transition (EndMT) in endothelial cells by regulating the expression of EndMT-associated TFs, such as Snail , Slug and Twist , as well as the TGF-β/Smad signaling pathway. The BRD4 inhibitors JQ1 and BRD4 knockdown significantly reversed the EndMT process in in vivo and ex vivo endothelial cells; blocked the synthesis of ECM proteins, such as α-smooth muscle actin(α-SMA), collagen I (COL I), and collagen III (COL III); and slowed cardiac fibrosis while preserving cardiac function [ 142 ]. Additionally, Zhangxu He et al. synthesized C-34, an inhibitor that targets BRD4 at the molecular and cellular levels. They discovered that by preventing the activation of the TGF-β/Smad signaling pathway, C-34 significantly reduces the proliferation and migration of neonatal rat cardiac fibroblasts (NRCFs) caused by angiotensin II (Ang II). This inhibition reduces the synthesis of ECM proteins, such as α-SMA, COL I and COL III, both in vivo and ex vivo. Consequently, C-34 effectively alleviates CFs activation and cardiac fibrosis in vivo, improving cardiac function [ 143 ]. These studies highlight the therapeutic potential of BRD4 inhibitors in treating cardiac fibrosis by targeting the molecular mechanisms underlying fibroblast activation and ECM synthesis. Deletion of the LMNA gene encoding laminin A/C in mouse cardiomyocytes is a common cause of DCM. It leads to cardiac dysfunction, fibrosis, ventricular arrhythmias, and other cardiac disorders. Gaelle Auguste demonstrated that treatment with the BRD4 inhibitor JQ1 partially reverses the transcript levels of molecular markers of cardiac hypertrophy and cardiac dysfunction in LMNA-deficient cardiomyocytes. It also reduces or normalizes the transcript levels of genes involved in fibrosis in the hearts of LMNA mice, ameliorates cardiac fibrosis, improves cardiac function, and prolongs the survival of cardiomyocyte-specific deletion LMNA mice [ 144 ]. These findings underscore the therapeutic potential of BRD4 inhibitors, such as JQ1, in treating various forms of cardiac fibrosis and dysfunction by targeting key molecular pathways involved in fibrosis and inflammation.

Inflammation is a pivotal factor in the progression of cardiac fibrosis. As indicated earlier, the interaction between BRD4 and NF-kB is important for regulating the expression of genes associated with inflammation. Research has demonstrated that upon stimulation with TNF-α, activated NF-κB rapidly enters the nucleus and recruits BRD4 to enhancers and promoters in the genome. The binding of BRD4 to NF-kB establishes a superenhancer regions and promotes the transcription of proinflammatory genes in a BRD4-dependent manner [ 145 ]. These findings suggest that BRD4 inhibition could provide indirect therapeutic benefits in cardiac fibrosis by ameliorating inflammation. Andrew Antolic et al. found in a mouse model of DCM that BRD4 was positively correlated with inflammatory genes induced by NF-kB in CFs. BRD4 mediates the expression of NF-kB-related inflammatory gene networks and fibrotic signaling networks through direct interaction with RelA. The BRD4 inhibitor JQ1 significantly suppressed CFs activation, adverse cardiac remodeling, and the extent of cardiac fibrosis [ 146 ]. Furthermore, Yiping Sun et al. confirmed that under hypoxic conditions, BRD4 binds to acetylated RelA in cardiomyocytes and is significantly recruited to the transcriptional promoters of NPPA and NPPB [ 147 ]. Interestingly, the inhibition of BET proteins has been found to mitigate cardiac damage in rats experiencing acute MI by modulating the TLR4/TRAF6/NF-kB pathway. This intervention reduces the enrichment of inflammatory cells in the infarcted area, improves cardiac remodeling, and reduces the infarct size [ 148 ]. Richard J. Mills et al. reported that the BET inhibitor INCB054329 blocked lipopolysaccharide (LPS)-induced proinflammatory cytokine production and exerted a preventive effect against inflammation-induced cardiac dysfunction in vitro and in vivo [ 149 ]. The BRD4 inhibitor JQ1 can upregulate silent information regulator 1 (SIRT1) expression in vitro and in vivo . This effect ameliorates LPS-induced cardiac inflammation and oxidative stress by inhibiting SIRT1-dependent activation of NOD-like receptor protein 3 (NLRP3) inflammatory vesicles [ 150 ]. JQ1 also enhances myocardial autophagy via the liver kinase β1 (LKB1)-AMPK-ULK1 signaling pathway; inhibits the release of inflammatory factors such as IL-6, IL-1β, TNF-α and interferon-γ (IFN-γ); and prolongs the survival time of allogeneic heart grafts [ 151 ]. Notably, Jinxia Han et al. showed that fucoxanthin (FX) inhibited Ang II-induced CFs transdifferentiation. This may be related to the fact that FX down-regulated the expression of BRD4 in CFs, reversed the inhibitory effect of Ang II on the downstream antioxidant signaling pathway of BRD4, nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1), and inhibited the increase in reactive oxygen species (ROS) and oxidative stress in CFs [ 152 ]. Another study revealed that during cardiac hypertrophy, ROS promoted BRD4 expression in mouse cardiomyocytes. BRD4 inhibition significantly reduced the prohypertrophic effects of Ang II on cardiomyocytes and significantly decreased the gene expression of fibrotic markers such as Tgfb1 , Col1a1 , Col1a3 and Ctgf . This also reversed the increase in P-NF-kB expression and the decrease in superoxide dismutase (SOD) activity caused by Ang II and aortic banding (AB) surgery while increasing the mRNA levels of Nrf-2 and HO-1. These findings suggest that BRD4 inhibition exerts cardioprotective effects through NF-κB signaling and the Nrf-2/HO-1 pathway [ 153 ]. These studies suggest that BRD4 inhibition is also capable of exerting an anti-cardiac fibrosis effect through oxidative stress pathways.

Myocardial fibrosis and apoptosis are significant features of diabetic cardiomyopathy. Hyperglycemia leads to the activation, proliferation, migration and synthesis of multiple ECM proteins in CFs and promotes the apoptosis of cardiomyocytes (H9C2) [ 154 ]. Relevant studies have confirmed that hyperglycemic stimulation elevates BRD4 expression levels in both H9C2 cells and CFs. The BRD4 inhibitor JQ1 can act on the TGF-β1/SMAD family member 3 (SMAD3) and protein kinase B (AKT) signaling pathways, attenuating the expression of fibrogenic genes such as Tgf-β , Ctgf , Col1α1 , Smad3 , and other fibrogenic genes in high-glucose (HG)-induced CFs. It also reduces the BAX/Bcl2 ratio in H9C2 cells, thereby exerting anti-fibrosis and anti-apoptotic effects [ 154 , 155 ]. In summary, BRD4 inhibition can exert anti-cardiac fibrosis effects by modulating multiple pathways related to fibrosis, inflammation and oxidative stress in cardiac effector cells, such as myocardial fibroblasts, cardiomyocytes and cardiac endothelial cells [Fig.  4 ].

Mechanisms of cardiac fibrosis involved in BRD4 and anti-cardiac fibrosis effects and mechanisms of BRD4 inhibitors. BRD4 is involved in fibrotic phenotypic changes in CFs, cardiomyocytes, and endothelial cells caused by external stimuli. It mainly affects the expression of fibrosis-related genes. BRD4 inhibitors (JQ1, C34, FX, and BEL) exert their anti-cardiac fibrosis effects mainly by inhibiting BRD4-mediated gene transcription, the TGF-β/Smad signaling pathway and oxidative stress

BRD4 in pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive, lethal, age-related lung disease [ 156 , 157 , 158 , 159 , 160 , 161 ]. The development of IPF involves multiple pathological processes. External stimuli causes damage to alveolar epithelial cells and subsequent lung inflammation [ 162 , 163 , 164 ]. Multiple cytokines in damaged lesions induce epithelial-mesenchymal transition (EMT) and fibroblast activation, which increases the proportion of myofibroblasts in the lungs and promotes myofibroblast synthesis of ECM and tissue repair [ 165 , 166 , 167 ]. However, when external stimuli persist, continuous damage to alveolar epithelial cells, ongoing lung inflammation, and persistent myofibroblast activation drive excessive and uncontrolled synthesis of the ECM [ 168 , 169 ]. This leads to excessive deposition of ECM in the lung interstitial space, resulting in destruction of the alveolar structure and severe impairment of gas exchange, which can ultimately cause respiratory failure and death [ 170 , 171 , 172 ]. Currently, only pirfenidone and nintedanib are approved by the FDA for the treatment of pulmonary fibrosis [ 173 , 174 , 175 ]. However, these drugs can slow disease progression but cannot stop or reverse it.

The critical role of the transdifferentiation and dedifferentiation of myofibroblasts in the progression of pulmonary fibrosis has been recognized by numerous researchers. Ksenija Bernau et al. used ZL0591, a highly selective variant inhibitor capable of binding specifically to BRD4 BD1, to assess the role of BRD4 in myofibroblast transdifferentiation. The i n vivo results revealed that ZL0591 reversed the increase in lung radiodensity after bleomycin (BLM) treatment and reduced the levels of α-SMA, Vim , Tnc , and Col1α1 in fibrotic lung tissues. These findings confirm that BRD4 BD1 inhibitors inhibit myofibroblast transdifferentiation and attenuate BLM-induced pulmonary fibrosis [ 176 ]. Consistent with these findings, KenicHi SuZuKi et al. found in vitro that JQ1 significantly inhibited the expression levels of α-SMA and fibronectin (FN) genes and proteins in myofibroblasts extracted from the lungs of patients with end-stage IPF. This inhibition induced the dedifferentiation of lung myofibroblasts. The manner in which JQ1 exerts its effects may involve the suppression of differentially expressed genes within signaling pathways associated with the ECM and fibrosis while promoting the expression of genes associated with glutathione metabolism [ 177 ]. Additionally, Seidai Sato et al. evaluated the therapeutic effect of ARV-825, a novel BRD4 degrader, on pulmonary fibrosis. They confirmed that ARV-825 reduced the expression of BRD4 and senescence markers and induced apoptosis in senescent cells. Moreover, ARV-825 inhibited the expression of fibrosis-associated proteins in TGF-β-stimulated nonsenescent cells, thereby attenuating BLM-induced pulmonary fibrosis [ 178 ]. These studies confirm that BRD4 is involved in the transdifferentiation of lung myofibroblasts and the progression of pulmonary fibrosis, suggesting its potential as a therapeutic target for pulmonary fibrosis.

What are the specific pathways by which BRD4 participates in the process of pulmonary fibrosis? Shunya Kaneshita et al. found that BRD4 was highly expressed in BLM-induced lung fibrotic lesions. Subsequent investigations demonstrated that within primary fibroblasts obtained from fibrotic mouse lungs, BRD4 exhibited notable enrichment in the promoter regions of the thrombospondin 1 ( Thbs1) , integrin β3 ( Itgb3) , and Acta2 genes. This enrichment promoted autocrine/paracrine TGF-β1 and pro-fibrotic actions associated with TGF-β1. In addition, the administration of CG223, a quinolone BRD4 inhibitor designed and synthesized by Shunya Kaneshita, significantly attenuated BLM-induced pulmonary fibrosis. It also decreased the mRNA levels of Thbs1 , Itgb3 , and Acta2 induced by TGF-β1 in primary lung fibroblasts (LFs), with the strength of the effect being dose dependent. Additionally, it decreases the expression of COL I, COL III, and α-SMA in myofibroblasts [ 179 ]. Similarly, TGF-β1 promotes the acetylation of H4K5 and the aggregation of BRD4 at the promoter regions of IL-6, plasminogen activator inhibitor-1 (PAL-1) and α-SMA. These findings suggest that TGF-β1 and BRD4 play complementary roles in the progression of pulmonary fibrosis. Xiaoyan Tang et al. found that the BET inhibitor JQ1 attenuated the TGF-β1 and PDGF-BB mediated migration and proliferation of LFs and reduced the expression of COL I and IL-6. The same results were obtained using BRD4 knockout [ 180 ]. Therefore, BRD4 inhibition could block the TGF-β1 signaling pathway to a certain extent, thus exerting an anti-pulmonary fibrosis effect. More excitingly, Bing Tian et al. discovered that polyinosinic:polycytidylic acid (poly I:C) could induce EMT in human small airway epithelial cell lines (hSAECs) [ 181 ]. BRD4 plays a role in stabilizing the transcription elongation complex during this process. Inhibitors of BRD4 significantly disrupt BRD4-HAT and RelA complex formation, preventing myofibroblast proliferation and attenuating fibrosis [ 182 ]. In addition, JQ1 treatment disrupted the enrichment of RelA, CDK9, and RNA Pol II at the promoters of EMT-associated TFs, such as SNAI1 , ZEB1 , IL-6 , and VIM. This suppressed the expression of mesenchymal genes, such as SNAI1 , FN1 , and VIM , induced by repetitive TGF-β1 stimulation. This inhibited TGF-β-induced epithelial fibrosis, expansion of mesenchymal supporting cells, thickening of alveolar septa and increased hydroxyproline content in the lungs of mice [ 183 ]. Other in vivo findings have shown that the BET inhibitor JQ1 also inhibits TGF-β1-dependent gene expression and BRD4 binding at the Gli1 promoter region in cancer-associated fibroblasts (CAFs), reducing fibroproliferation and cancer cell proliferation [ 184 ]. Taken together, BRD4 contributes to pulmonary fibrosis disease progression by participating in multiple signaling pathways involved in TGF-β/Smad signaling.

The ROS-generating enzyme NOX4 and the antioxidant enzyme SOD2 are central to the regulation of intracellular ROS. Moreover, redox dysregulation is a key factor in the induction of LFs activation. Previous studies have shown that the gene expression of NOX4 is significantly increased, whereas the expression of SOD2 is significantly inhibited in human fibrotic LFs. Further research revealed that BRD4 binds to the NOX4 promoter and is involved in the TGF-β-induced gene expression of NOX4. This mechanism explains the ability of the BRD4 inhibitors JQ1 and OTX015 to inhibit the binding of BRD4 to the NOX4 promoter and reduce the enrichment of H4K16ac and P300 at the NOX4 gene promoter. This resulted in reduced protein and gene expression of NOX4 in primary IPF LFs and in TGF-β1-induced normal human embryonic LFs (IMR90). Additionally, these inhibitors inhibit the TGF-β-induced increase in NOX4 and ACTA2 and the reduction in SOD2 while increasing Nrf2 activity, thereby reducing the level of ROS in cells and fibroblast activation and promoting the regression of pulmonary fibrosis in mice [ 185 , 186 ]. Collectively, this evidence suggests that BRD4 is involved in promoting NOX4 expression and mediating oxidative stress-induced pulmonary fibrosis. Like its effects on cardiac fibrosis, JQ1 was found to reduce the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) in a dose-dependent manner, thereby reversing the inflammation and fibrosis progression in the lungs caused by BLM treatment [ 187 ]. These findings suggest that BRD4 inhibition similarly ameliorates the progression of fibrosis in the lungs by attenuating inflammation. Interestingly, Bing Tian et al. found that repetitive mucosal cat dander extract (rCDE) stimulation triggered BRD4-HAT and phosphorylated RNA Pol II kinase activity by activating NF-kB/RelA, leading to the acetylation of Lys122 on histone H3 [ 188 ]. Airway fibrosis, EMT and myofibroblast expansion induced by rCDE are dependent on BRD4 function. Treatment with Zl0454, a small molecule inhibitor of BRD4, reduced mucosal H3K122 acetylation accumulation and the expression of snail family transcriptional repressor 1 (SNAI1), vimentin (VIM), FN, COL I, and α-SMA [ 188 ]. However, the exact mechanisms by which BRD4 inhibition ameliorates pulmonary fibrosis by suppressing inflammation remain to be further explored.

BET protein inhibition is also a therapeutic for radiation-induced lung fibrosis (RILF). Chunshan Liu et al. found that iBET-BD2 (GSK046) is an inhibitor that selectively targets the second bromodomain of BET proteins. It was able to attenuate radiation-induced fibroblast fibrin marker expression [ 189 ]. Similarly, Jian Wang et al. demonstrated that JQ1 administration significantly attenuated inflammatory infiltration, fibrosis and collagen deposition in the lungs caused by irradiation. Further assays revealed that JQ1 administration reduced the radiotherapy-induced expression of BRD4, c-MYC, COLI, TGF-β, P65, and p-Smad2/3. The transdifferentiation of human LFs to myofibroblasts resulting from radiation treatment was similarly inhibited by JQ1 [ 190 ]. Furthermore, in addition to its significant involvement in inflammation, oxidative stress, and fibrosis in pulmonary fibrosis, BRD4 has also been associated with various other lung-related diseases. Notably, BRD4 expression levels are elevated in the blood and sputum of patients with chronic obstructive pulmonary disease (COPD). BRD4 was positively correlated with the expression of IL-6 and interleukin-8 (IL-8) in bronchial epithelial cells (BEAS-2B cells) following exposure to cigarette smoke and viral infection [ 191 ]. MiR-218 attenuated cigarette smoke extract-mediated secretion of the inflammatory factors TNF-α, IL-6, and IL-8 in bronchial epithelial cells by targeting and inhibiting the expression of BRD4 [ 192 ]. Zhen Xiao et al. demonstrated that JQ1 may delay the progression of COPD by increasing the expression of agrin protein [ 193 ]. In addition, JQ1 blocked the nuclear translocation and acetylation of P65 and inhibited the binding of P65 to DNA in the lung tissues of mice with COPD. JQ1 administration improved inflammation, oxidative stress, and lung function in the lung tissues of mice in a dose-dependent manner, exerting a protective effect against COPD [ 194 , 195 ]. During TLR3-NFkB/RelA-mediated airway remodeling, BRD4 inhibitors block the pericyte-to-myofibroblast transition, protecting vascular homeostasis and reducing vascular leakage [ 196 ]. BRD4 expression is elevated in patients with idiopathic pulmonary arterial hypertension (PAH) and promotes the upregulation of polo-like kinase 1 (PLK1) via forkhead box M1 (FoxM1). RVX208 inhibits proliferation, promotes apoptosis, ameliorates inflammation through the BRD4-FoxM1-PLK1 axis in PAH-associated vessels, and improves vascular remodeling and pulmonary hemodynamics in rats in vivo [ 197 ]. In summary, we concluded that BRD4 can serve as a target in pulmonary fibrosis and has the potential to serve as a therapeutic target in lung diseases such as airway remodeling, interstitial lung disease, PAH and COPD [ 198 ]. BRD4 inhibition effectively mitigates the progression of pulmonary fibrosis and COPD while also ameliorating PAH and acute lung injury [Fig.  5 ].

Mechanisms of pulmonary fibrosis involved in BRD4 and anti-pulmonary fibrosis effects and the mechanisms of BRD4 inhibitors. BRD4 is involved in fibrotic phenotypic changes in lung fibroblasts (LFs) and epithelial cells caused by external stimuli. It mainly affects the expression of fibrosis-related genes. BRD4 inhibitors (JQ1, ZL0591, CG233, OTX015, and ARV-825) exert their anti-pulmonary fibrosis effects mainly through the inhibition of BRD4-mediated gene transcription, the activation of LFs, the EMT process and oxidative stress

BRD4 in hepatic fibrosis

Chronic alcoholic liver disease, inflammation, hepatitis viral infection, cholestasis and many other diseases that cause liver injury can induce hepatic fibrosis [ 69 , 199 , 200 ]. Hepatic fibrosis eventually progresses to cirrhosis or hepatocellular carcinoma (HCC), leading to liver failure and death if the onset and progression of hepatic fibrosis are not controlled in a timely manner. HSCs are the main precursor cells of myofibroblasts in the liver and are quiescent under physiological conditions [ 201 , 202 ]. Liver injury induced by various external stimuli results in hepatocyte necrosis and cytokine release [ 203 ]. This allows HSCs to be activated to gain the ability to proliferate, migrate and synthesise ECM for tissue repair. Long-term liver injury leads to permanent activation of myofibroblasts, which is out of the control of the body's repair mechanism. This results in continuous secretion of ECM and excessive deposition of ECM gradually destroys the normal tissue structure and physiological function of the liver. As a result, liver tissue is gradually replaced by fibrous tissue, leading to the progressive formation of abnormal scar tissue and liver remodeling [ 204 ].

Several studies have shown that BRD4 is abnormally elevated in hepatic fibrosis tissues caused by various etiologies such as viral hepatitis infections (hepatitis C virus (HBV), hepatitis C virus (HCV)), non-alcoholic steatohepatitis (NASH), autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), cholestasis, and alcohol-associated liver disease (ALD) [ 205 , 206 ]. BRD4 has been detected predominantly in hepatocytes, activated HSCs [ 207 ], macrophages and biliary cells. The expression of BRD4 is positively correlated with the severity of hepatic fibrosis as well as alanine transaminase (ALT) and aspartate transaminase (AST) levels in HBV-induced hepatic fibrosis [ 206 ]. These findings suggest that BRD4 may be involved in the development of hepatic fibrosis. Research has demonstrated that BRD4 has the capacity to facilitate the progression of liver fibrosis via various pathways. First, Ning Ding et al. demonstrated that BRD4 binds to the COL1A1 enhancer site and is significantly enriched at the motifs of pro-fibrotic TFs, such as ETS proto-oncogene 1 (ETS1), serum response factor (SRF), SMAD3, and NF-kB. BRD4 is able to participate in the transcriptional regulation of pro-fibrotic genes through enhancer progenitors. In addition, BRD4 is able to directly target the PDGF pathway as a mitogenic regulator of HSCs proliferation. The presence of JQ1 inhibits the expression of genes involved in cell activation during primary HSCs activation, suggesting that BRD4 has the potential to be an anti-fibrosis target [ 208 ]. Second, similar to its role in pulmonary fibrosis, BRD4 synergistically promotes with the TGF-β signaling pathway in hepatic fibrosis. Feifan Xu et al. found that BRD4 is involved in the effects of TGF-β1 on the PDGF receptor and the SMAD3, signal transducer and activator of transcription 3 (STAT3) and AKT pathways. TGF-β1-induced increases in the expression of histone acetyltransferase P300, NF-kB P65, and tissue inhibitor of metalloproteinase 1 (TIMP1) require the participation of BRD4 [ 209 ]. At the same time, TGF-β1 significantly upregulated the protein and gene expression levels of BRD4 in HSCs. The mechanism involves TGF-β1-induced activation of the STAT3 signaling pathway, which promotes the expression of the early-immediate gene (Egr1). TGF-β1 further facilitates the binding of Egr1 to the BRD4 promoter, thereby promoting the expression of BRD4, leading to HSCs activation and hepatic fibrosis. Furthermore, Egr1 also has a positive feedback effect on STAT3 activation. Knockdown of BRD4 blocks the induction of HSCs activation and hepatic fibrosis via STAT3 signaling [ 210 ]. In terms of other signaling pathways, Xiaobo Cai et al. found that BRD4 is involved in the activation of HSCs bychemokine (C-X-C motif) ligand 6 (CXCL6). CXCL6 was able to enhance the interaction of SMAD3 with BRD4, BRD4 with the C-MYC promoter, and C-MYC with the enhancer of zeste homolog 2 (EZH2) promoter via the SMAD2/BRD4/C-MYC/EZH2 pathway, inducing the activation of quiescent HSCs into myofibroblasts [ 211 ]. Additionally, Jinhang Gao et al. demonstrated that BRD4 is involved in TNF-α-induced P300/NF-κB/BRD4 transcriptional activator complex formation and CCL2 transcription. TNF-α leads to acetylation of histone H3K27 in the enhancer and promoter regions of the CCL2 gene via P300. Increased CCL2 expression with the involvement of the epigenetic reader BRD4 leads to hepatic fibrosis and portal hypertension [ 212 ]. Miao Cheng et al. further confirmed that BRD4 knockdown in mice with CCl 4 -induced hepatic fibrosis significantly reduced the degree of fibrosis and suppressed the expression of fibrosis-associated genes. This mechanism may be related to the involvement of P300 in the PLK1 promoter in H3K27 acetylation, and BRD4 promotes PLK1 expression by recognizing and binding to acetylated H3K27 [ 213 ]. Moreover, BRD4 also binds to acetylated P65 (lysine 310) in the NF-kB signaling pathway in mouse macrophages while exerting a pro-inflammatory effect [ 214 ]. Additionally, USP22, a deubiquitylating protease, is able to interact with and reduce the ubiquitylated level of BRD4 to promote the inflammatory response in ALD involving BRD4 [ 205 ]. Taken together, these findings suggest that BRD4 can serve as an effective target against hepatic fibrosis.

JQ1 is a classical small molecule inhibitor of BRD4. JQ1 has been found to reduce BRD4 enrichment at the COL1A1 enhancer site, decrease the expression of pro-fibrotic genes in HSCs, inhibit their activation, and prevent and reverse CCl 4 -induced fibrosis in the mouse liver [ 208 ]. Additionally, JQ1 was able to bind the bromodomain of P300 and inhibit its acetyltransferase activity. In turn, it treats S. japonicum-infected induced hepatic fibrosis in mice by inhibiting RORγt acetylation and decreasing the expression of Th17-specific cytokines [ 215 ]. Hepatic injury is a predisposing factor for hepatic fibrosis. JQ1 attenuates hepatic necrosis, inflammation and mitochondrial dysfunction by inhibiting the expression of receptor-interacting protein kinase 1 (RIPK-1) through the BRD4/RIPK1 axis [ 216 ]. Abnormalities in lipid metabolism contribute to the development of hepatic fibrosis. Aki Yamada and colleagues reported that excessive fructose intake led to increased acetylation of histones H3 and H4. This facilitated the enrichment of BRD4 in the transcriptional areas of genes associated with lipid accumulation ( Cyp8b1 , Dak , and Plin5 ), which increased expression of genes linked to lipid accumulation. JQ1 treatment attenuated the effects of fructose overdose on the above pathological processes [ 217 ]. Another study showed that JQ1 upregulated PD-L1 expression in HCC cells by increasing Rab8A expression, thus promoting the immunotherapeutic effect of an anti-PD-L1 antibody on HCC cells [ 218 ]. In addition to JQ1, other BRD4 inhibitors have been used to treat hepatic fibrosis. Sarah A. Middleton et al. evaluated the effects of the small molecule inhibitor of the BET protein GSK1210151A (I-BET151) on NASH and hepatic fibrosis. They found that I-BET151 treatment was able to maintain glucose homeostasis, reduce the expression of inflammatory genes in the interferon signaling pathway, and inhibit the expression of Tgf-β , Timp1 and other fibrosis-related genes [ 219 ]. Rong Fu et al. synthesized a BET inhibitor, Compound 38, based on ABBV-075 (one of the most potent inhibitors of the BET bromodomain). They found that compound 38 attenuated inflammatory cell infiltration in the liver as well as the expression of pro-inflammatory factors such as IL-6, TNF-α, and IL-1β in macrophages via the JAK-STAT and MAPK signaling pathways. It further alleviated the liver injury and inflammation caused by LPS/GalN injection. Meanwhile, compound 38 inhibited the activation of HSCs and exerted antifibrotic effects through the TGF-β/SMAD and Wnt/β-catenin signaling pathways [ 220 ]. Yanwen Lan et al. reported that salvianolic acid A (SAA), an active ingredient in Salvia miltiorrhiza, could effectively act on the BRD4/high mobility group box 1 (HMGB1) pathway. It inhibited the translocation of HMGB1 by down-regulating BRD4 expression, reduced the expression of ethanol-induced inflammatory factors such as IL-6, IL-1β, and TNF-α, and attenuated ethanol-induced liver injury [ 221 ]. Simplicity acid (SA) is a phenolic acid that binds specifically to BRD4 and alleviates alcohol-induced liver injury by attenuating oxidative stress and pyroptosis [ 222 ]. In addition, Ying Hsien Huang et al. demonstrated that microRNA-29a overexpression reduced BRD4 and SNAI1 expression in a BDL-induced hepatic fibrosis model. MicroRNA-29a overexpression was also able to down-regulate the expression of EZH2 and SNAI1 in primary HSCs and increase peroxisome proliferator-activated receptor-γ (PPAR-γ) expression, which inhibited the migration and proliferation of HSCs [ 223 ]. The down-regulation of BRD4 by microRNA-29a was further confirmed by Yen-Cheng Lin et al. [ 224 ]. HCC is the result of the progression of hepatic fibrosis to the end stage. Cho-Hao Line et al. reported that a bivalent BRD4 inhibitor, AZD5153, was able to inhibit the expression of pro-carcinogenic genes associated with BRD4, inhibit the proliferation of hepatocellular carcinoma cells and promote their apoptosis [ 225 ]. In summary, BRD4 can serve as an effective target for treating hepatic fibrosis, and BRD4 inhibition can significantly attenuate the progression of hepatic fibrosis through TGF-β, inflammation and other signaling pathways [Fig.  6 ].

Mechanisms of hepatic fibrosis involved in BRD4 and anti-hepatic fibrosis effects and mechanisms of BRD4 inhibitors. BRD4 is involved in fibrotic phenotypic changes in hepatic stellate cells (HSCs), epithelial cells, macrophages and hepatocytes caused by external stimuli. It mainly affects the expression of fibrosis-related genes. BRD4 inhibitors (JQ1, Compound 38, SAA) exert their anti-hepatic fibrosis effects mainly by inhibiting BRD4-mediated gene transcription, activation of HSCs, and expression of inflammatory factors

BRD4 in renal fibrosis

Chronic kidney disease (CKD) is a chronic fibrotic disease that results from the progression of renal fibrosis to the later stages of the disease. Renal fibrosis is the ultimate pathological process shared by chronic kidney injury or adaptive repair [ 226 ]. Oxidative stress [ 227 , 228 ], inflammation [ 229 ], lupus nephritis [ 230 ], hypertensive nephropathy (HN) [ 231 ], diabetic nephropathy [ 232 ], acute kidney injury (AKI) [ 233 ], and renal ischemia–reperfusion injury (IRI), among many other renal disorders, can lead to renal injury, which can trigger renal fibrosis. Myofibroblasts are the primary producers of ECM in the kidneys [ 234 ]. When the kidneys are subjected to various external stimuli, pericytes [ 235 , 236 ], mesenchymal stem cell-like cells, macrophages [ 237 , 238 ], epithelial cells [ 239 ], and perivascular fibroblasts in the kidneys transform into myofibroblasts. These myofibroblasts participate in the repair of damaged kidney tissues and produce large amounts of ECM, leading to the onset of renal fibrosis [ 240 , 241 ].

Several studies have shown that BRD4 is upregulated in a variety of renal diseases, including hyperuricemia nephropathy [ 242 ], focal segmental glomerulosclerosis (FSGS), LgA nephropathy [ 243 ], renal IRI [ 244 ], unilateral ureteral obstruction(UUO) renal injury [ 245 ], HN [ 246 ], diabetic kidney disease (DKD) [ 247 ], and renal cell carcinoma (RCC) [ 248 ]. These findings indicate that BRD4 might be involved in the pathogenesis of various renal diseases and could serve as a promising therapeutic target for managing renal fibrosis. In terms of renal fibrosis and kidney injury, progressive glomerulonephritis (GN) is characterized by excessive deposition of collagen IV (COL IV) in the glomeruli and glomerulosclerosis. José Luis Morgado Pascual et al. examined the effect of JQ1 on GN in a murine model of nephrotoxic serum (NTS)-induced anti-glomerular basement membrane nephritis. JQ1 attenuated NTS-induced accumulation of COL IV in glomeruli and glomerulosclerosis and alleviated UUO-induced sex-determining region Y-box 9 (SOX9) nuclear translocation and renal interstitial fibrosis. Mechanistically, JQ1 can block the TGF-β1/Smad signaling pathway, attenuate the binding of BRD4 to the Col4a3 promoter, and inhibit the activation and nuclear translocation of SOX9 in the kidneys of NTS-treated mice [ 249 ]. Similarly, Sandra Rayego Mateos et al. showed that JQ1 inhibited the expression of pro-fibrotic factors (TGF-β, connective tissue growth factor (CTGF), PAI-1) and the progression of renal fibrosis in UUO-treated kidneys. JQ1 reduced ECM-associated components (FN and COL I) in TGF-β-treated mesangial cells and renal fibroblasts and inhibited the nuclear translocation of SOX9 [ 250 ]. Additionally, JQ1 inhibited the expression of α-SMA, COL III, and FN at the gene and protein levels in Ang II-induced HN kidneys. It also reversed EMT and attenuated Ang II-induced renal injury and renal fibrosis [ 246 ]. Maria Laura Saiz et al. encapsulated JQ1 in liposomes and found that liposome-loaded JQ1 attenuated IRI-induced AKI, inflammation and renal fibrosis and improved pharmacokinetics and toxicity [ 251 ]. Inflammation is a significant contributor to the pathogenesis of renal fibrosis, and a variety of renal inflammatory diseases are predisposing factors for renal fibrosis. As mentioned above, BRD4 can directly bind to RelA and induce the release of inflammatory factors associated with the NF-kB pathway. BRD4 can also bind directly to the gene promoters of CCL2 , CCL5 , and IL-6 , mediating the expression of pro-inflammatory factors. Suarez Alvarez, Beatriz et al. demonstrated that JQ1 hindered the interaction between BRD4 and the promoters of RelA and genes associated with inflammation. JQ1 administration counteracted TNF-α-induced increases in the pro-inflammatory factors CCL2, C–C motif chemokine ligand 5 (CCL5) and IL-6 in human renal tubular epithelial cells (HK2 cell line). Moreover, JQ1 reduced the infiltration of inflammatory cells and the expression of inflammatory cytokines, chemokines (C–C motif chemokine ligand 20 (CCL-20), chemokine (C-X-C motif) ligand 16 (CXCL-16), and adhesion molecules (intercellular adhesion molecules (ICAM-1)) in a renal fibrosis model and a renal inflammation model. Additionally, JQ1 suppressed Th17 immune responses in renal inflammation, leading to decreased renal inflammation and injury, improved glomerular lesions, and the restoration of renal function [ 252 ]. Zhong Gui Gong et al. found that cadmium (Cd) promotes the acetylation of lysine at position 310 in RelA and the binding of BRD4 to acetylated RelA K310, inducing the activation of the NF-kB inflammatory signaling pathway. JQ1 treatment or BRD4 knockdown significantly inhibited the Cd-induced nuclear translocation of NF-kB in vitro and in vivo . This further attenuated the transcription of inflammatory cytokines (IL-1β, IL-6, TNF-α, and monocyte chemotactic protein-1 (MCP-1)) in Cd-treated rat kidneys and NRK-52E cells, thereby attenuating Cd-induced inflammation in rat kidneys [ 253 ]. In addition, BRD4 knockdown or JQ1 treatment inhibited the phosphorylation of NF-kB and promoted NLRP3 transcription through the NF-kB/NLRP3/caspase-1 signaling pathway. NLRP3 is able to mediate caspase-1-dependent pyroptosis in RCC cells, thereby inhibiting the proliferation and EMT of RCC cells [ 248 ]. In terms of oxidative stress, BRD4 is involved in TGF-β1-induced oxidative stress and fibrogenic gene expression. Baoshang Zhou et al. demonstrated that JQ1 inhibited Nox4 transcription through the TGF-β/Smad signaling pathway and the extracellular signal regulated kinase 1/2 (ERK1/2) pathway, thereby attenuating NOX4-mediated oxidative stress. Furthermore, JQ1 was able to reduce α-SMA and FN deposition in the renal mesenchyme caused by UUO and prevent the progression of renal fibrosis in rats [ 245 ]. BRD4 also promotes forkhead box protein O4 (FOXO4) transcription by inhibiting the phosphorylation of the PI3K/AKT signaling pathway. This promotes FOXO4-induced oxidative stress and contributes to hypoxia-reoxygenation (HR) in vitro and to IRI in vivo mediated apoptosis and endoplasmic reticulum stress (ERS). BRD4 inhibition via JQ1 or BRD4 siRNA protects against kidney injury caused by renal IRI [ 244 ]. Liping Sun et al. found that JQ1 treatment significantly inhibited cisplatin-induced apoptosis in renal proximal tubular cells and AKI. This mechanism may be related to the fact that JQ1 attenuates CHK2-mediated DNA damage and reduces cisplatin-induced P53, as well as the phosphorylation of P38, ERK1/2, and c-Jun N-terminal protein kinase (JNK) in the MAPK signaling pathway. Interestingly, JQ1 treatment reversed the induction of the antioxidant proteins Nrf2 and HO-1 by cisplatin and inhibited the expression of inducible nitric oxide synthase (iNOS) in nitrosative stress, thereby attenuating cisplatin-induced oxidative stress in the kidney [ 254 ]. Cd promoted the acetylation of H4K16, which is involved in autophagy and lysosomal gene expression. It also promoted BRD4 enrichment at the histone H4K16 locus and inhibited the transcriptional levels of lysosomal genes. This leads to lysosomal dysfunction and autophagy blockage, which further leads to oxidative stress and cytotoxicity. JQ1 or BRD4 knockdown significantly restored lysosomal-mediated autophagy and reduced Cd-induced oxidative stress and cytotoxicity, thereby protecting against Cd-induced AKI [ 255 ]. In summary, BRD4 plays an important role in promoting renal fibrosis. BRD4 may be an effective target for treating renal fibrosis. The BRD4 inhibitor JQ1 can exert anti-renal fibrosis effects through three pathways: attenuation of renal injury, inflammation and oxidative stress.

Given the importance of BRD4 in the development of renal fibrosis, researchers have investigated the therapeutic effects of other BRD4 inhibitors for renal disease. Chongxiang Xiong et al. evaluated the therapeutic effects of IBET151, a small molecule inhibitor of the BET protein, on renal fibrosis. They found that while down-regulating the renal levels of BRD4, I-BET151 effectively suppressed the activation of various signaling pathways, including the TGF-β/Smad3, STAT3, ERK1/2, and NF-kB pathways, and inhibited the phosphorylation of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR). Additionally, I-BET151 decreased the expression of C-MYC, TNF-α, MCP-1, and P53 and reversed EMT in the kidneys. I-BET151 further reduces the activation of renal mesenchymal fibroblasts and the deposition of α-SMA, COL I and FN, ameliorating renal fibrosis [ 242 , 243 ]. HIV infection in the kidney induces NF-kB activation, which triggers inflammation. Guangtao Zhang et al. reported that the BRD4 inhibitor MS417 can competitively bind tightly to the bromodomain of BRD4 and block the binding of BRD4 to NF-kB. This inhibited the transcriptional activation of pro-inflammatory cytokines and chemokines related to the NF-kB pathway in the kidney, such as CCL2 , CCL3 , CCL5 , CCL20 , and TLR-2. MS417 also inhibited the expression of pro-apoptotic genes, such as NF-kB-targeted BCL2 , FAS , and TRAF1 , and attenuated inflammatory cell infiltration and glomerular and tubular injury caused by HIV infection [ 256 ]. Meanwhile, MS417 inhibited oxidative stress-induced IL-6 expression and significantly reduced CCL2 expression and the number of centrocytes in the kidneys of IRI mice, thereby attenuating tubular damage caused by IRI [ 257 ]. Sibei Tao et al. reported a new BRD4 inhibitor, ZLD2218. In vivo administration of ZLD2218 at 30 mg/kg/day for eight consecutive days significantly inhibited BRD4 levels in fibrotic kidneys. Importantly, ZLD2218 blocked UUO-induced activation of the TGF-β/Smad3 signaling pathway and suppressed α-SMA, COL I, COL IV and FN expression, significantly attenuating renal fibrosis and renal injury [ 258 ]. Apabetalone (RVX-208), an oral BET inhibitor used for treating cardiovascular disease, has also shown promise for treating renal disease. Sylwia Wasiak et al. demonstrated that RVX-208 downregulated CKD-related protein markers and molecular pathways in the plasma of renal injury patients. It reduces IL-6, interleukin-17 (IL-17), IL-12 and other plasma protein levels of inflammation-related cytokines and down-regulated the levels of plasma proteins associated with the NF-kB signaling pathway in CKD patients [ 259 ]. Min Wang et al. found that BRD4 can activate the NLRP3 inflammasome through the P300/H3K27ac/PLK1 axis, which in turn triggers cellular death and inflammation in the kidney. RVX-208 down-regulates the protein level of BRD4 and attenuates renal injury and fibrosis in DKD [ 247 ]. The above studies further confirmed that BRD4 can be a promising target against renal fibrosis and that BRD4 inhibition has a therapeutic effect on renal fibrosis [Fig.  7 ].

Mechanisms of renal fibrosis involved in BRD4 and anti-renal fibrosis mechanisms of BRD4 inhibitors. BRD4 is involved in the fibrotic phenotypic changes in tethered cells and parietal epithelial cells caused by external stimuli. BRD4 inhibitors (JQ1, I-BET151, ZLD2218, and MS417) mainly inhibit BRD4-mediated gene transcription and oxidative stress to exert anti-renal fibrosis effects

BRD4 inhibitors in organ fibrosis

To date, there are approximately 1700 inhibitors that target BRD4. Given the role of BRD4 in the development of fibrogenesis, BRD4 inhibitors have significant potential for use in treating organ fibrosis. However, only approximately a dozen BRD4 inhibitors are currently used in preclinical studies of organ fibrosis. Here, we summarize the BRD4 inhibitors that are currently being used in studies of organ fibrosis. The aim of this review was to provide a reference for the in-depth application of BRD4 inhibitors in organ fibrosis.

RVX208 is an orally administered quinazolinone BET inhibitor [ 260 ]. In preclinical studies, RVX-208 has been shown to ameliorate PAH and DKD [ 197 , 247 ]. Early clinical studies focused on exploring the safety of RVX-208 in healthy individuals and patients (NCT00768274, NCT01058018) and its therapeutic efficacy in PAH (NCT03655704). RVX208 has now progressed to clinical phase III trials for reducing adverse cardiovascular events in patients with type 2 diabetes mellitus and coronary artery disease (NCT02586155) [ 261 ]. OTX015 (MK-8628), a triazolo benzodiazepine BET inhibitor [ 262 ], is currently in clinical trials to explore its appropriate dose range in patients with hematological malignancies (NCT01713582) and advanced solid tumors (NCT02259114) [ 263 , 264 , 265 , 266 , 267 , 268 , 269 ]. In organ fibrosis, OTX015 was able to inhibit the binding of BRD4 and NOX4 promoters, reducing ROS levels in fibroblasts and attenuating pulmonary fibrosis in mice [ 186 ]. JQ1, the first BET inhibitor, is a thieno-triazolo-1,4-diazepine synthesized by Panagis Filippakopoulos et al. in 2010. JQ1 binds highly specifically to the bromodomain of the BET family, occupying the acetylated lysine-binding pocket of BRD4 and interfering with BRD4 and histone acetylated lysine binding [ 270 ]. In organ fibrosis, JQ1 has been extensively used to explore the role of BRD4 in fibrotic disease progression. Current studies have shown that JQ1 is able to exert therapeutic effects on organ fibrosis through various pathways, such as reversing the EndMT and EMT processes, blocking the TGF-β and NF-kB signaling network pathways, reversing the oxidative stress imbalance, inhibiting BRD4 binding to the NOX4 promoter, inhibiting myofibroblast activation, inhibiting BRD4 enrichment at the promoters of fibroblastic genes, and reducing inflammatory cytokine expression. I-BET151 is an imidazolidinone-based selective inhibitor of BET [ 271 , 272 ], which has good bioavailability in rats and minipigs [ 273 ]. In preclinical studies, I-BET151 has been shown to inhibit the activation of the TGF-β/Smad3, STAT3, ERK1/2, and NF-kB signaling pathways in renal fibrosis and to reverse renal EMT [ 242 , 243 ]. In hepatic fibrosis, I-BET151 is able to maintain glucose homeostasis and reduce the expression of inflammatory genes in the interferon signaling pathway, thus exerting a therapeutic effect on hepatic and renal fibrosis [ 219 ]. MS417, an inhibitor of BRD4, blocks the binding of BRD4 to acetylated RelA, thereby inhibiting the expression of genes associated with the NF-kB pathway [ 256 , 274 , 275 ]. In CKD, MS417 hinders the transcriptional activation of pro-inflammatory cytokines and chemokines linked to the NF-kB pathway, leading to a decrease in the expression of IL-6 and CCL2, thereby attenuating the infiltration of inflammatory cells and glomerular injury [ 257 ]. C-34, a phenylquinazoline-based BRD4 inhibitor synthesized by Wen Zhao's group, has been shown to block the activation of the TGF-β1/Smad2/3 signaling pathway, inhibit fibroblast activation, and ameliorate cardiac fibrosis [ 143 ]. CG223, a quinolone-based BET inhibitor, inhibits the TGF-β signaling pathway to exert an anti-fibrotic effect on pulmonary fibrosis [ 179 ]. ZL0454, a BRD4-selective inhibitor with cyclopentylbenzenesulfonamide scaffolding developed by Allan R. Brasier et al., blocks the NF-kB signaling pathway and attenuates inflammatory responses triggered by external stimuli, improving airway remodeling [ 188 , 276 ]. ZL0591 was synthesized by Zhiqing Liu et al. and is a selective mutational inhibitor that targets BRD4 BD1. The in vivo half-life of ZL0591 was significantly prolonged relative to that of ZL0454 [ 277 ]. ZL0591 has been shown to significantly ameliorate pulmonary fibrosis [ 176 ]. ARV-825 is a novel BET degrader. As a heterobifunctional protein hydrolyzes targeting chimeras, it can effectively induce the binding of E3 ubiquitin ligases to the BET family and degrade BET family proteins [ 278 ]. ARV-825 has demonstrated good preclinical antifibrotic effects against pulmonary fibrosis [ 178 ]. Compound 38 is a derivative optimized on the basis of the structure of ABBV-075 by Zizhou Li et al. [ 279 ]. It is capable of attenuating the hepatic inflammatory response through the JAK-STAT and MAPK signaling pathways. In addition, compound 38 also exerts anti-hepatic fibrotic effects through the TGFβ/SMAD and Wnt/β-catenin signaling pathways [ 220 ]. ZLD2218 is a BRD4 inhibitor of pyrrolidinones, which was obtained by Sibei Tao et al. on the basis of the structural optimization of ABBV-075, INCB057643, I-BET151 and PLX51107, and it was able to significantly reduce BRD4 levels in fibrotic kidneys and block the TGF-β/Smad3 signaling pathway to exert an anti-kidney fibrotic effect [ 258 ]. In summary, these BRD4 inhibitors have shown significant potential in treating various forms of organ fibrosis [Table  1 ]. Continued studies of these inhibitors could further elucidate the therapeutic potential of BRD4 in fibrotic diseases.

Conclusions and perspectives

Organ fibrosis is a condition in which external stimuli lead to changes in epigenetic and gene expression within cells, changes in fibroblast morphology and function, transformation into myofibroblasts, and excessive synthesis of ECM by myofibroblasts, leading to structural damage and dysfunction of organs. Epigenetics is significantly involved in the pathogenesis of organ fibrosis [ 31 ], and BRD4 is an epigenetic reader that translates histone modification changes caused by external stimuli into gene expression changes, thus linking external stimuli to pathological changes in cells. Given the importance of BRD4 in diseases such as cancer, inflammation and fibrosis, this review introduces current research progress on BRD4 in organ fibrosis. Importantly, multiple studies have demonstrated the significant involvement of BRD4 in fibrosis development. Utilizing BRD4 inhibitors or reducing BRD4 expression has been shown to mitigate the progression of organ fibrosis [ 142 , 183 , 213 , 242 , 243 ]. BRD4 is involved mainly in the expression of genes related to fibrosis, inflammation, EMT, EndMT, and oxidative stress during the progression of organ fibrosis and is able to bind to enhancers and super-enhancers of fibrosis-related genes, which in turn promotes the progression of fibrotic diseases. In addition, BRD4 inhibitors may also significantly slow the progression of organ fibrosis by acting on non-classical TGF-β/Smad signaling pathways, such as the PI3K/AKT, JAK/STAT, Wnt/β-catenin, and MAPK pathways [Fig.  8 ]. Therefore, we believe that BRD4 has potential as an anti-fibrotic target. However, the specific mechanism of action of BRD4 in the development of fibrosis is currently unknown and needs to be further explored. In current preclinical studies, BET inhibitors are mostly used to study the mechanism of BRD4 in organ fibrosis, which makes it difficult to exclude the influence of other BET proteins on the fibrotic disease process, and the use of selective inhibitors of BRD4 to study the mechanism of BRD4 in organ fibrosis may become an important direction of research in the future [ 261 ]. In addition, we present the challenges of BRD4 inhibitors in fibrotic diseases. BRD4 as an epigenetic reader, we need to focus on the function of BRD4 in normal cells and tissues under physiological conditions and explore the effects of BRD4 inhibition or absence on normal tissues and organs. Soo Young Kim et al. found that cardiomyocyte BRD4 is important for maintaining myocardial function and myocardial energy homeostasis [ 280 ]. In the liver, some researchers have found that BET proteins are involved in hepatocyte proliferation and liver regeneration [ 281 ]. The ability of the BRD4 inhibitor JQ1 to significantly inhibit hepatocyte regeneration suggests that we need to pay attention to the timing of the use of JQ1 in the treatment of hepatic fibrotic diseases and to avoid the use of JQ1 in the stage of rapid hepatocyte regeneration[ 282 ]. Similarly, Julia Wilflingseder et al. and Janina Schreiber et al. found that BRD4 is involved in renal growth, development, and repair and that the use of the BET inhibitor JQ1 may lead to renal hypoplasia. The administration of JQ1 before renal injury inhibited renal repair and led to renal failure, whereas the administration of JQ1 2–7 days after renal injury inhibited excessive renal repair and ameliorated renal interstitial fibrosis, suggesting that BET inhibitors may have potential teratogenic effects [ 283 , 284 ]. In summary, in clinical studies, we need to focus on the duration of dosing and the teratogenic effects of BRD4 inhibitors. On the basis of the current understanding of BRD4 in organ fibrosis, some researchers have begun to explore the combined effects of BRD4 inhibitors and other drugs. Raghda Hassan et al. found that JQ1 and atorvastatin synergistically inhibited hepatic stellate cell activation [ 285 ]. However, Hyunkyung Jung et al. showed that the BRD4 inhibitor JQ1 has an antagonistic effect on FXR agonists (OCA) [ 286 ]. These findings suggest that we need to be equally aware of the use of BRD4 inhibitors in combination with other drugs.

Mechanism of BRD4 involvement in organ fibrosis and mechanism of action of BRD4 inhibitors. BRD4 can bind to fibrosis-related enhancers and super-enhancers. BRD4 is involved mainly in the expression of TGF-β1-associated fibrosis genes, NF-kB-associated inflammatory genes, EMT-associated genes, EndMT-associated genes and oxidative stress-associated genes. BRD4 inhibitors primarily exert their antifibrotic effects by suppressing the expression of genes linked to the progression of fibrosis. Furthermore, BRD4 inhibitors can demonstrate anti-fibrotic properties through the suppression of the non-canonical TGF-β signaling pathway[ 67 ]

Approximately 1700 BRD4 inhibitors are available, and only a dozen BRD4 inhibitors have been used in organ fibrosis studies. Pelabresib, a selective inhibitor of BRD4, is in phase III clinical trials [ 287 ] for the treatment of myelofibrosis (NCT04603495), but no relevant studies have reported the therapeutic role of Pelabresib in organ fibrosis. RVX-208, a BET inhibitor, is in clinical phase III studies for the improvement of cardiovascular disease and has been reported to have an ameliorative effect on organ fibrosis in preclinical studies, and it is expected to be a potential drug for the treatment of organ fibrosis. In addition, CPI-0610 [ 288 , 289 ], BMS-986158 (NCT05372354, NCT04817007) [ 290 ], BMS-986378 [ 291 ], ABBV-075 [ 292 , 293 ], ABBV-744 [ 294 , 295 ], and other BRD4 inhibitors are also in the clinical research stage. Fibrosis is an over-repairing disease that is difficult to reverse, and there are no clinically available drugs for treating cardiac, hepatic or renal fibrotic diseases. Various BRD4 inhibitors have shown promising antifibrotic effects in preclinical studies. Appropriate doses for the treatment of fibrotic diseases can be found on the basis of available clinical trial data on BRD4 inhibitors, which are used in subsequent fibrotic clinical trials. If BRD4 inhibitors show promising therapeutic effects in clinical studies of fibrosis, this would be a major breakthrough in the treatment of fibrotic disease and could lead to significant cost savings in fibrotic drug development. In addition, the green channel mechanism for orphan drugs for fibrotic diseases will significantly shorten the review and approval cycle for fibrotic therapeutics, and if BRD4 inhibitors have the effect of reversing or slowing the progression of fibrosis in clinical trials, they will provide more options for the treatment of fibrosis in the clinic.

Availability of data and materials

No datasets were generated or analysed during the current study.

Abbreviations

Aortic banding

Autoimmune hepatitis

Acute kidney injury

Protein kinase B

Alcohol-associated liver disease

Alanine transaminase

Angiotensin II

Atrial natriuretic peptide

Aspartate transaminase

Bronchoalveolar lavage fluid

Bromodomains

Bellidifolin

Bromodomain and extra-terminal structural domain

Base-interacting structural domain

Brain natriuretic peptide

Bromodomain

Bromodomain-containing protein 2

Bromodomain-containing protein 3

Bromodomain-containing protein 4

Histone acetyltransferase activity of BRD4

Bromodomain testis-specific protein

Cancer-associated fibroblasts

Cycle-dependent kinase 9

Cardiac fibroblasts

Chronic kidney disease

C-C motif chemokine ligand 2

C-C motif chemokine ligand 5

C-C motif chemokine ligand 20

Collagen III

Collagen IV

Chronic obstructive pulmonary disease

C-terminal phosphorylation site

C-terminal domain

Connective tissue growth factor

C-terminal motif

Chemokine (C-X-C motif) ligand 6

Dilated cardiomyopathy

Diabetic kidney disease

Extracellular matrix

Epidermal growth factor receptor

Early-immediate gene

Epithelial-mesenchymal transition

Endothelial-to-mesenchymal transition

Extracellular signal regulated kinases ½

Endoplasmic reticulum stress

Extra-terminal

ETS proto-oncogene 1

Enhancer of zeste homolog 2

Fibronectin

Forkhead box M1

Forkhead box protein O4

Focal segmental glomerulosclerosis

Fucoxanthin

Glomerulonephritis

Histone acetyltransferases

Hepatitis B virus

Hepatocellular carcinoma

Hepatitis C virus

Histone deacetylases

Heme oxygenase-1

High-glucose

High mobility group box 1

Hypertensive nephropathy

Human small airway epithelial cell lines

Hypoxia-reoxygenation

Hepatic stellate cells

Human umbilical vein endothelial cells

Intercellular adhesion molecule

Interferon-γ

Interleukin-6

Interleukin-1β

Interleukin-8

Interleukin-17

Inducible nitric oxide synthase

Idiopathic pulmonary fibrosis

Ischemia-reperfusion injury

Isoprenaline

Integrin β3

C-Jun N-terminal protein kinase

Lung fibroblasts

Lipopolysaccharide

Mouse aortic endothelial cells

Mitogen-activated protein kinase

Monocyte chemotactic protein-1

Myocardial infarction

Non-alcoholic steatohepatitis

NADPH oxidase 4

NOD-like receptor protein 3

N-terminal phosphorylation site

Neonatal rat cardiac fibroblasts

Nuclear factor erythroid 2-related factor 2

Nephrotoxic serum

Pulmonary arterial hypertension

Plasminogen activator inhibitor-1

Poly (ADP-ribose) polymerase-1

Primary biliary cholangitis

Platelet-derived growth factor

Platelet-derived growth factor receptor

P-TEFb interaction domain

Polo-like kinase 1

Peroxisome proliferator-activated receptor-γ

Positive transcription elongation factor b

Renal cell carcinoma

Repetitive mucosal cat dander extract

Radiation-induced lung fibrosis

Receptor-interacting protein kinase 1

RNA polymerase II

Reactive oxygen species

Simplicity acid

Salvianolic acid A

α-Smooth muscle actin

Silent information regulator 1

SMAD family member 3

Snail family transcriptional repressor 1

Small nuclear ribonucleoprotein

Superoxide dismutase

Sex-determining region Y-box 9

Serum response factor

Signal transducer and activator of transcription 3

Transverse aortic constriction

Transcription factors

Transforming growth factor β

Thrombospondin 1

Tissue inhibitor of metalloproteinase 1

Tumor necrosis factor-α

Unilateral ureteral obstruction

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This study was supported by the National Natural Science Foundation of China (82370076), Sichuan Science and Technology Program (2023NSFSC0525), The Clinical Research Innovation Project, West China Hospital, Sichuan University (2019HXCX005), Open competition mechanism to select the best candidates for key research projects of Ningxia Medical University (XJKF230121).

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Qun Wei and Cailing Gan contributed equally to this work.

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Laboratory of Gastrointestinal Cancer and Liver Disease, Department of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China

Qun Wei, Cailing Gan, Meng Sun, Yuting Xie, Hongyao Liu, Taixiong Xue, Conghui Deng & Tinghong Ye

Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China

Chunheng Mo

Ningxia Medical University, Yin Chuan, 640100, China

Tinghong Ye

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Q.W. wrote and revised the manuscript. C.G. and M.S. prepared the figures. Y.X., H.L., T.X., and C.D. revised the manuscript. C.M. and T.Y. edited and reviewed the manuscript. All authors read and approved the final manuscript.

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Wei, Q., Gan, C., Sun, M. et al. BRD4: an effective target for organ fibrosis. Biomark Res 12 , 92 (2024). https://doi.org/10.1186/s40364-024-00641-6

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Received : 05 July 2024

Accepted : 16 August 2024

Published : 30 August 2024

DOI : https://doi.org/10.1186/s40364-024-00641-6

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• Organ fibrosis
• Signaling pathways
• BRD4 inhibitor

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