Human beings are really too weak when it comes to regenerative abilities…

In superhero movies, regeneration is a powerful skill point. No matter what damage you take, you will be able to revive with full health and continue fighting in a short while. Like

Deadpool, he can grow back with broken hands, broken feet, and hearts and lungs.

Hands and feet can grow again even broken

Ordinary people of course also have some regenerative abilities, such as the liver. Even if a healthy person donates 2/3 of the liver, the remaining 1/3 can 0lkm?e regenerated and returned to normal size within a few months.

But unfortunately, the heart, which is vital to human beings, cannot be regenerated.

Our heart is made up of cardiomyocytes. These cells maintain the beating of the heart, and if they are damaged, the function of the heart can be permanently impaired, and in severe cases can even lead to death. At present, cardiovascular disease is the leading cause of death in the world; in my country, there are about 330 million people suffering from cardiovascular disease.

The important heart does not have the ability to regenerate, if the heart can be regenerated, it can save many lives

If the heart can also gain the ability to regenerate, it may be possible 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 have found sentinels in the brain and kidneys of the zebrafish, which are extremely regenerative, to warn against cardiac trauma. The damaged heart uses hormones to inform sentinels in the brain and kidneys to work in concert with distant organs to regulate heart regeneration and coordinate various physiological changes in the process, according to a study published in Nature Cell Biology.

Amazing zebrafish

The phenomenon of organ regeneration is not uncommon in nature. For example, polyps and planarians only need to retain a very small part of the tissue to regenerate a complete body, but zebrafish is the darling of scientists to study the ability of regeneration.

First of all, zebrafish has many important organs that can be regenerated, such as the heart, spinal cord, and fins (corresponding to human limbs). Understanding the regeneration process of these organs can help people better study related diseases and develop treatment plans.

As vertebrates, zebrafish also have many of the same major organs as mammals, so researchers can not only study the regeneration capacity of specific organs, but also understand how different organs communicate and cooperate during the regeneration process.

From an evolutionary point of view, the similarity between zebrafish and humans is not low, and more than 70% of human genes correspond to zebrafish. Therefore, studying zebrafish can be a good reference for humans.

Similar to humans, and with strong regeneration ability, zebrafish is the most suitable for research.

How does the heart regenerate?

Cardiomyocytes in adults have no regenerative capacity. When the human heart is damaged, there will be some fibrotic scar tissue, which affects the beating of the heart.

When a person’s heart is damaged, kidney problems can also occur. The kidney is the “blood filter” in our body, it filters out excess water and waste in the blood to form urine, and at the same time regulates our body’s water-salt balance and controls 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, kidney damage, and even kidney failure.

The zebrafish’s heart regeneration ability is much stronger. When its heart is damaged, the remaining cardiomyocytes will begin to reproduce themselves and re-grow the lost parts; at the same time, the kidneys can also quickly self-regulate and efficiently liquid exchange.

From top to bottom are the zebrafish brain, heart, and kidneys

After the human heart is damaged, the kidneys can only wait for disaster to come; and the heart and kidneys of zebrafish are already connected efficiently. For them, how did the distant kidneys get the news of the heart damage and respond in time?

Kidney Sentinels work together

The researchers of the paper found that when the heart is injured, a sentinel CEN in the kidney awakens its challenge mechanism to actively control fluid balance in response to the damage caused by the heart injury.

Heart: help…

The sentinel CEN is a DNA sequence, the scientific name is “tissue regeneration enhancer” (TREE, tissue regeneration enhancer elements).

Every cell of an organism has the same genetic material DNA, but why do the same genes show different appearances and functions in cells?

Because under different circumstances, 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 control gene expression by binding to proteins.

When “enhancers” are open to welcome guests, they can bind to proteins and promote gene expression; when they are closed, the gene expression level will be relatively low. Therefore, tissue regeneration enhancers are DNA sequences that control the process of tissue regeneration, and CEN is one of them.

When CEN opens to welcome guests, it can combine with protein to promote gene expression

When the heart is injured, CEN will open its arms to meet the binding of the proteins, thereby directly and indirectly controlling the expression of many genes, activating and mobilizing various cardiac cells to achieve the purpose of cardiac regeneration.

However, unlike other tissue regeneration enhancers, CEN’s action is not limited to the heart during cardiac regeneration — CEN in the kidney is also turned on. At the same time, hormones in the body will reach the kidneys, activate their receptors, and then combine with the open CEN to promote the expression of specific genes in the kidneys, actively regulate fluid balance, and respond to the crisis brought about by heart injury.

Without CEN, can zebrafish heart regeneration go so smoothly?

The researchers used gene editing technology to delete the CEN sequence from the DNA of zebrafish. They found that zebrafish that lost the sentinel could still regrow their hearts, but they couldn’t regulate fluid exchange properly. This may be because there are other “sentinels” in the heart that can control the regeneration of cardiomyocytes, and in the kidneys, the function of CEN is irreplaceable.

If humans can make better use of regenerative power, human health will improve a big step

Regeneration does not mean that the injured organ is fighting alone, and the organ that has not been directly injured will also respond, which can be said to affect the whole body. If humans could better harness the power of regeneration to repair damaged organs—whether it’s the heart, kidneys, liver, or hands and feet, it could save countless lives and improve the quality of life for countless others.

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