TRP离子通道在牵张力诱导的人胚胎干细胞分化的心肌细胞成熟中的作用

项目名称： TRP离子通道在牵张力诱导的人胚胎干细胞分化的心肌细胞成熟中的作用

项目编号： No.31470912

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 姚晓强

作者单位： 香港中文大学深圳研究院

项目金额： 90万元

中文摘要： 本研究主要集中在TRP通道在周期性牵张力作用下对人胚胎干细胞分化来的心肌细胞成熟的机制，对于干细胞治疗具有重大的意义。瞬时感受器电位通道（TRP）是一类重要的阳离子通道家族，并被认为是心肌细胞感知机械牵张和渗透压改变的重要感受器。但是TRP通道在人胚胎干细胞分化的心肌细胞中的作用还不清楚。因此，揭示人胚胎干细胞分化来的心肌细胞在牵张力的作用下成熟信号途径和机制，对于干细胞治疗心血管相关疾病具有重要的意义。本课题旨在研究（一）阐明哪一种TRP离子通道在周期性牵张力作用下调控心肌细胞Ca2+信号转导和心肌细胞成熟。（二）构建TRP离子通道的慢病毒表达载体，并转染人胚胎干细胞分化的心肌细胞，来研究过表达或降低TRP通道蛋白表达对心肌细胞成熟的影响。 (三）我们还将对TRP离子通道激活的具体机制和路径作进一步的研究。研究成果可为将来能否以TRP通道作为干细胞治疗的靶点提供重要的理论依据。

中文关键词： TRP；离子通道；牵张力；心肌细胞成熟

英文摘要： The research focuses on the role of transient receptor potential channels (TRP) in regulation of hESC-derived ventricular cardiomyocytes (hESC-VCM) mature in response to cyclic stretch. Fundamental understanding of hESC-derived ventricular cardiomyocytes mature mechanisms help us to grasp the process of the development of cardiomyocyte and to find the key regulation of stem cell therapy which has great significance. TRP channels are Ca2+-permeable non-selective cation channels. These channels are regarded as environmental sensors in many types of cells, which is thought to be involved in sensing osmolarity and membrane stretch. However, their roles in hESC-derived ventricular cardiomyocytes (hESC-VCMs) are still unknown. In vivo cardiomyocytes are faced to cyclic stretch. Therefore, to reveal cardiomyocyte mature signaling pathways and mechanisms under mechanical stretch has important implications for the prevention and treatment of cardiovascular disease using stem cell. However, most important problems in this research area have been unresolved. These problems include which TRP channel plays an important role in the cyclic stretch induced cardiomyocyte maturation process; the possibility of using the inhibition of TRP channels as a means to regulate cardiomyocytes maturation. The purpose of this project is to study: (1) which TRP channel play a role in the regulation of cardiomyocyte in response to cyclic stretch and Ca2+ signal transduction and cardiomyocyte maturation in response to cyclic stretch; (2) In order to confirm the functional role of TRP in regulation of hESC-derived ventricular cardiomyocytes, we will construct several TRP plasmids into chronic virus (lentivirus) expression vector separately, and transfected human embryonic stem cell differentiation of cardiomyocytes for overexpression or reducing TRP expression. (3) We will explore how the TRP channel function in stretch-induced cardiomyocyte maturation for further study. These results of this research will provide an important theoretical basis for TRP channel as a regulatory target for stem cell therapy.

英文关键词： TRP ion channel;stretch;cardiomyocyte maturation