A gene called Meis1 regulates the heart’s ability to regenerate after injuries, according to researchers at UT Southwestern Medical Center. The laboratory of Hesham Sadek, M.D., Ph.D., assistant professor of internal medicine in the division of cardiology, previously showed that the newborn mammalian heart is capable of a vigorous, regenerative response to injury through division of its own cells. As the newborn develops, the heart rapidly loses the ability to regenerate and to repair injuries such as heart attacks.
Now, the research team demonstrated that deletion of Meis1 extended the proliferation period in the hearts of newborn mice, and also re-activated the regenerative process in the adult mouse heart without harmful effect on cardiac functions. The scientists also found that overexpression of Meis1 in cardiomyocytes decreased neonatal myocyte proliferation and inhibited neonatal heart regeneration.
This new finding demonstrates that Meis1 is a key factor in the regeneration process, and the understanding of the gene’s function may lead to new therapeutic options for adult heart regeneration. The findings also provide a possible alternative to current adult heart regeneration research, which focuses on the use of stem cells to replace damaged heart cells.
“We found that the activity of the Meis1 gene increases significantly in heart cells soon after birth, right around the time heart muscle cells stop dividing. Based on this observation we asked a simple question: If the Meis1 gene is deleted from the heart, will heart cells continue to divide through adulthood? The answer is ‘yes’,” says Dr. Sadek.
The team discovered that Meis1 is required for transcriptional activation of the synergistic CDK inhibitors p15, p16, and p21. “Meis1 is a transcription factor, which acts like a software program that has the ability to control the function of other genes. In this case, we found that Meis1 controls several genes that normally act as brakes on cell division,” Dr. Sadek explains. “As such, Meis1 could possibly be used as an on/off switch for making adult heart cells divide. If done successfully, this ability could introduce a new era in treatment for heart failure.”
The study was published online yesterday in Nature, in a paper titled “Meis1 regulates postnatal cardiomyocyte cell cycle arrest”.