组蛋白去甲基化酶JMJD3在促成年心肌细胞增殖中的作用及其机制研究

成年心肌细胞（adult cardiomyocyte, ACM）损伤后缺乏自我更新的能力，是心肌梗死后心力衰竭的重要原因。如何使ACM再分裂从而修复心肌是当前再生医学中的热点。c-Myc是一种调控细胞周期进程的重要转录因子，可促进ACM重新进入细胞周期，但无法再分裂，其中机制不明。我们初步研究提示组蛋白去甲基化酶JMJD3参与了c-Myc促ACM重新进入细胞周期这一过程，并且与心肌细胞分裂密切相关，因此推测JMJD3可能是c-Myc诱导ACM进入细胞周期却无法分裂的瓶颈。本项目拟进一步阐明JMJD3促ACM再分裂的作用，并利用心肌特异性JMJD3转基因小鼠心肌梗死模型，体内阐明JMJD3促进ACM再分裂修复心肌的作用，并深入探讨其分子机制。本项目可能解决我们目前对于心脏再生知识的关键缺陷，将为创新一种可促进ACM再生修复的手段提供实验研究基础。

Adult cardiomyocyte (ACM)cell cycle exit is the most important reason for post-myocardial infarction heart failure.Myocardial regeneration to restore cardiac muscle mass after injury is a means to prevent the development of heart failure.c-Myc can induce ACM cell cycle reentry but not mitosis and the mechanism is unclear. Our preliminary data suggest that histone demethylase JMJD3 is critical for cardiomyocyte proliferation and involvoed in c-Myc regulation of ACM cell cyle.This project will explore the effect of JMJD3 on ACM proliferaiton and the underlying molecular mechanism with myocardial infarction model of JMJD3 transgenic mice. We may figure out the defects of our current knowledge of cardiac regeneration and will provide experimental research base for innovative means to promote ACM sel-renew and myocardial regeneration.