microRNAs通过调控细胞周期影响心肌再生的研究进展

Role of MicroRNAs in Myocardial Regeneration by Regulating Cell Cycle Activity

心肌细胞丢失是缺血性心脏病导致患者预后不良的重要病理生理学过程。现已发现,成人心脏中心肌细胞存在有限的自我增殖更新能力。在斑马鱼、鼠等模式动物建立的心肌再生模型中,成年期心肌细胞经诱导后可发生有丝分裂、增殖再生,而激活细胞周期是促进心肌再生的关键环节。本文拟综述心肌细胞中细胞周期激活因子(细胞周期蛋白和细胞周期素依赖性蛋白激酶)、抑制因子(p21、p27、p57、p16和p18)和细胞周期相关蛋白(Rb、p107和p130)在心肌再生中的变化及作用,并讨论microRNAs对心肌再生过程中细胞周期的影响,以期为心肌再生方面的研究提供一定参考。

Loss of cardiomyocytes is the main pathophysiological process responsible for the poor prognosis of patients with ischemic heart disease. It has been demonstrated that cardiomyocytes in adult humans have a limited ability of self-renewal and proliferation. Recent studies have found that adult cardiomyocytes underwent mitosis and proliferation to regenerate after the re-initiation of cell-cycle activity based on multiple heart regeneration models, such as zebrafish and mice. These findings suggested that the modulation of the cardiomyocyte cell cycle may be a key step in successful myocardial regeneration. In this review, we discussed the effect of cell cycle activators(cyclins and CDKs), inhibitors(p21, p27, p57, p16, and p18), and cell-cycle-associated proteins(Rb, p107, and p130) on cardiac regeneration. Furthermore, we collected evidence from recent studies which investigated the role of microRNAs on cell cycle during myocardial regeneration. Our work may provide basis for further studies into myocardial regeneration.