Hepatocyte growth factor (HGF) promotes cardiac stem cell differentiation after myocardial infarction by increasing mTOR activation in p27(kip) haploinsufficient mice

摘要

Myocardial infarction (MI) is a major cause of death worldwide. The treatment of MI has improved during the last decade; however, the loss of myocytes remains a problem because the cells cannot be renewed. Cardiac stem cells were recently discovered and were thought to represent a promising treatment for MI. However, the efficiency of cardiac stem cell differentiation into myocyte is not sufficient. Hepatocyte growth factor (HGF) is related to the differentiation and proliferation of cardiac stem cells. p27(kip1) is a potent cell cycle inhibitor in most organs, especially the heart. In this study, we investigated the relationship among p27, HGF and cardiac stem cells in post-MI cardiac repair. We found that p27 haploinsufficient mice exhibited preserved cardiac function and improved cardiomyocyte renewal compared with wild-type mice. In addition, p27 haploinsufficiency may not increase cardiac stem cell proliferation but could improve their differentiation by increasing mammalian target of rapamycin expression.