项目名称: Neuregulin-1/miR-200c信号通路在小鼠胚胎干细胞心肌分化及亚型选择中的作用
项目编号: No.81200119
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 医学一处
项目作者: 陈明
作者单位: 武汉大学
项目金额: 23万元
中文摘要: 胚胎干细胞源性心肌细胞(ESC-CM)包含工作样细胞和起搏样细胞,其用于心肌梗死后的移植,起搏样细胞会形成异位起搏点,增加不良心律失常的发生率及移植后的死亡率,因此需要对如何控制ESC-CM的亚型分化,增加工作样细胞比例进行深入的研究。神经调节蛋白(NRG)-1能够促进ESC-CM向工作样细胞分化,但作用机制不详,且尚未见其对移植后疗效影响的报道。我们前期研究结果提示NRG-1与miR-200c之间可能存在反馈环路,共同调控心肌细胞亚型分化。本研究拟通过细胞实验验证miR-200c对ESC-CM亚型分化的影响,NRG-1与miR-200c之间存在反馈环路且共同调控ESC-CM亚型分化;动物实验验证ESC-CM通过调控NRG-1/miR-200c信号,移植入心肌梗死大鼠模型后,能够降低移植后的死亡率,改善心功能及增加电生理稳定性。本研究旨在为心肌梗死后干细胞移植提供更有效和更安全的分化策略。
中文关键词: 胚胎干细胞;神经调节蛋白-1;miR-200c;心肌细胞;亚型
英文摘要: Embryonic stem cells-derived cardiomyocytes(ESC-CMs) include working-like and pacemaker-like phenotypes. It is necessory to control ESC-CMs subtype specification for infarct repair, as the pacemaker-like cardiomyocyte could form ectopic rhythm and increase the risk of malignant arrhythmias and post-transplant mortality. Neuregulin-1(NRG-1) is involved in the course of ESC-CMs subtype specification, which promotes the working-like cardiomyocyte differentiation. Whereas the underlying mechanisms are poorly understood. Our previous studies indicate that NRG-1 can regulate the expression of miR-200c and miR-200c may regulate the expression of NRG-1 in turn. We suppose that there is a feedback loop between NRG-1 and miR-200c, both of which control the subtype differentiation of ESC-CM. To test this hypothesis,we will perform the following experiments:① investigate the effects of NRG-1/miR-200c on the subtype differentiation of ESC-CM and whether or not there is a feedback regulation between NRG-1 and miR-200c in vitro.② transplant ESC-CMs treated with NRG-1/miR-200c into the rat model of myocardial infarction and observe post-transplant mortality, heart funcition, the electrophysiology stability,and so on. Our studies aim to find a more precise target of differentiation,and to provide a more effective and safer diff
英文关键词: embryonic stem cells;neuregulin-1;miR-200c;cardiomyocyte;subtype