Scientists at Southwest University in Texas have revealed the molecular mechanism of heart regeneration in mammals, which have grown most of their hearts after injury: newborn mice.
These newborns kept the secret of ventricular tissue regeneration about 15% for a long time, and this ability occurred in a short window period of about 7 days after birth. Once this window is closed, the heart cells will mature and the rats will never be able to regenerate the damaged heart area.
This research is being carried out at the Harmon Center for Regenerative Science and Medicine of the university, where scientists have published a series of breakthrough research results on heart regeneration. 20 1 1 year, Texas researchers cooperated with another American team to announce for the first time in the world that these animals can regenerate a large number of heart tissues. Mice restart their hearts by regenerating new cardiomyocytes, which are responsible for the strong contractility of healthy organs.
Now, in a new development, scientists have determined that genes, their protein products and a series of cells, including macrophages in the immune system, participate in the regeneration process. Team members said that this progress may one day provide a way to help people get sick.
"Our work provides a detailed molecular blueprint for heart regeneration in newborn mice, and provides rich resources for identifying genes that may help repair injured hearts," said Wang Zhaoning, the first author of the team's latest research report. Published in the Proceedings of the National Academy of Sciences. Wang said that research is very important because it may have an impact on the potential applications of human beings. Heart disease is the leading cause of death all over the world. Once damaged, the contracted cells will not regenerate. In a heart attack, an adult's heart may lose as many as 654.38 billion cardiomyocytes, because these cells will not proliferate, which means that they will not replenish themselves. Wang said that the absence of myocardial cells will lead to decreased myocardial contractility, scar formation and heart failure.
In contrast, the heart of newborn mice can effectively regenerate healthy tissues and make organs play an effective role in the later stage. Wang said that animals lose this ability after the first week of life because the regenerated components are "mature in structure and function". "The newborn's heart experienced rapid development in the first week after birth, that is, within the regeneration time window," said Wang, a researcher in Dr. Eric Olson's laboratory.
"We found that during this time window, the genes involved in heart development were active, but when the heart exited this time window, they quickly weakened. This shows that the newborn heart uses this short developmental genetic program in the process of heart regeneration, "he said." In other words, the hearts of mice injured in the first few days of life can regenerate heart tissue, because animals still retain the "embryonic cardiogenic gene program" and cannot recover after seven days.
Although fractures can be repaired and skin, hair and millions of cells are constantly replaced, human organs can not be regenerated except the liver. In addition to this ability, another noteworthy form of human regeneration is that some very young children can regenerate their fingers if their nails remain intact after injury. Other species also have dramatic regenerative abilities: sharks constantly change the teeth of their killers; Spiders can replace lost legs, and lizards can reproduce most or all of them. Mexican salamander, commonly known as salamander, can greatly regenerate limbs and organs.
Wang and his colleagues have obtained the most in-depth data about mammalian heart regeneration, although it is a tiny organ of newborn mice. In their research, they deeply studied the transcription group of animals-the sum of all messenger RNA in the mouse genome. They also analyzed histone, a protein found in eukaryotic nuclei that helps DNA packaging.
"The transcriptome of newborn heart is a collection of whole mRNA," Wang said. These mRNA carry genetic information synthesized directly from DNA to protein. By studying the transcriptome, we can directly identify the genes expressed in the process of heart regeneration. ""Histones are protein that combine with DNA to form chromatin, "he added, referring to the biological materials that make up chromosomes. He said that histone, like transcriptome, has an influence on the molecular environment involved in the regeneration of injured heart.
Wang and his team made more discoveries when comparing the hearts of 7-day-old regenerated and unregenerative mice. They found that the regenerative heart with sustained injury produced a unique immune response. The most prominent is a factor called CcL24 released by macrophages, which can promote regeneration. The RNA binding protein IGF-2bp3 still exists in the regeneration process.
"We have determined that CcL24 and Igfbp3 are previously uncharacterized regulatory factors of cardiomyocyte proliferation, which may have potential therapeutic significance," Wang said. "By providing this resource to this website, we hope it can promote the understanding of the mechanism of neonatal heart regeneration and find more therapeutic targets for human heart disease," he said. # Breeze Project #