In superhero movies, regeneration is a powerful skill point. No matter what damage you take, you can resurrect with blood and continue fighting for a while. Like the lowly Deadpool, severed hands and feet, digging out the heart and lungs can grow again.
Broken hands and feet can also continue to grow| Giphy
Ordinary people of course also have some regenerative abilities, such as livers, even if a healthy person donates 2/3 of the liver, the remaining 1/3 can be regenerated within a few months and return to normal size.
But unfortunately, the heart that is vital to people cannot be regenerated.
Our heart is made up of cardiomyocytes. These cells maintain the beating of the heart, and once they are damaged, the function of the heart is permanently damaged, and in severe cases, it can even lead to death. Cardiovascular disease is currently the leading cause of death worldwide; on the mainland, about 330 million people are also affected by cardiovascular disease.
Important hearts do not have the ability to regenerate, and if they can regenerate, they can save many lives| Giphy
If you can make the heart also gain the ability to regenerate, you may be able to find a way to overcome cardiovascular disease.
To uncover the secrets of the heart's ability to regenerate, American biologist Kenneth Poss and his team found sentinels in its brain and kidneys that warned against heart trauma by studying the zebrafish, which is extremely regenerative. Damaged hearts use hormones to notify sentinels in the brain and kidneys, work in tandem with distal organs, regulate heart regeneration, and coordinate various physiological changes in the process, the study was published in Nature Cell Biology.
Magical zebrafish
Organ regeneration is not uncommon in nature, such as hydras and planarians that only need to retain a very small part of the tissue to re-grow a complete body, but zebrafish are the darlings of scientists studying regenerative ability.
An adult female zebrafish | Azul
First of all, zebrafish have many important organs that can be regenerated, such as the heart, spinal cord, and fish fins (corresponding to human limbs), and understanding the regeneration process of these organs can help people better study related diseases and develop treatment options.
As a vertebrate, zebrafish also have many major organs like mammals, so researchers can not only study the regenerative ability of specific organs, but also understand how different organs communicate and cooperate in the process of regeneration.
From an evolutionary point of view, the similarity between zebrafish and humans is not low, and more than 70% of human genes are corresponding in zebrafish. Therefore, the study of zebrafish can be a good reference for humans.
Similar to humans, and has a strong regenerative ability, zebrafish is the most suitable for research.
How is the heart regenerated?
Adult cardiomyocytes do not have the ability to regenerate. When the human heart is damaged, some fibrotic scar tissue will appear, affecting the beating of the heart.
When a person's heart is damaged, the kidneys can also have problems. The kidneys are the "blood filters" in our bodies, which filter out excess water and waste in the blood to form urine, while regulating the balance of water and salt in our bodies and controlling blood pressure. When the heart is damaged, it may lead to a series of problems such as insufficient blood flow to the kidneys, increased blood pressure in the renal veins, damaged kidneys, and even kidney failure.
When its heart is damaged, the remaining cardiomyocytes will begin to multiply and re-grow the lost part; at the same time, the kidneys can quickly self-regulate and efficiently exchange fluids.
From top to bottom, zebrafish brain, heart, kidneys | references[1]
After the human heart is damaged, the kidneys can only sit and wait for the disaster to come; and the zebrafish's heart and kidneys have been efficiently connected, for them, how do the distant kidneys get the news of heart damage and respond in time?
Kidney sentries fight together
The researchers found that when the heart is injured, a sentinel in the kidney, CEN, awakens its response mechanism to actively control the fluid balance in response to the harm caused by the heart injury.
Heart: Save me... ｜Giphy
The sentinel CEN is a DNA sequence scientifically called a "tissue regeneration enhancer elements" (TREE).
Every cell of an organism has the same genetic material DNA, but why do the same genes, cells, behave and function differently?
Because in different cases, cells can perform different functions by expressing different genes. "Enhancers" are one of the ways cells control gene expression. Enhancers are specific DNA sequences that can control the expression of genes by binding to proteins.
When the "enhancer" opens to welcome customers, they can bind to proteins and promote gene expression; and when they close behind closed doors, the expression of genes will be relatively low. Therefore, tissue regeneration enhancers are some DNA sequences that control the process of tissue regeneration, and CEN is one of them.
When CEN opens to welcome guests, it can bind to proteins and promote gene expression| Giphy
When the heart is injured, CEN will open its arms to welcome the binding of proteins, thereby directly and indirectly controlling the expression of many genes, activating and mobilizing various heart cells to achieve the purpose of heart regeneration.
However, unlike other tissue regeneration enhancers, in the process of heart regeneration, the scope of CEN is not limited to the heart - the CEN in the kidneys will also be turned on. At the same time, the hormones in the body will reach the kidneys, activate their receptors, and then bind to the open CEN, promote the expression of specific genes in the kidneys, actively regulate fluid balance, and cope with the crisis caused by heart injury.
Without CEN, can zebrafish's heart regeneration go so smoothly?
The researchers used gene editing techniques to remove the SEQUENCE OF CEN from the zebrafish's DNA. They found that zebrafish, which had lost the sentry, could still grow their hearts again, but could not regulate fluid exchange normally. This may be because there are other "sentinels" in the heart that can control the regeneration of cardiomyocytes, while in the kidneys, the function of CEN is irreplaceable.
If humans make better use of their regenerative abilities, human health will be a big step | Giphy
Regeneration is not the injured organ fighting alone, and the organ that has not been directly injured will also react, which can be described as a whole body. If humans can make better use of their regenerative power to repair damaged organs— whether hearts, kidneys, livers, or hands and feet — they can save countless lives and improve the quality of life for countless people.
bibliography
[1] Sun, F., Ou, J., Shoffner, A.R. et al. Enhancer selection dictates gene expression responses in remote organs during tissue regeneration. Nat Cell Biol (2022). https://doi.org/10.1038/s41556-022-00906-y
[2] Cardiac regeneration strategies: Staying young at heart https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614484/
[3] In the face of the "number one killer", how not to be "sad" http://www.news.cn/mrdx/2021-09/30/c_1310219361.htm
[4] Zebrafish cells taught me about regeneration| The amazing regenerative capabilities of zebrafish | Chen-Hui Chen | TEDxTaipeihttps://www.youtube.com/watch?v=PGx3i9_vhZ0
Author: Hazel
Editor: Small towel, you zhiyou
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