MiR-139-5p通过调控Rho/ROCK信号通路参与高血压心肌重塑

项目名称： MiR-139-5p通过调控Rho/ROCK信号通路参与高血压心肌重塑

项目编号： No.81460068

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 杨晓敏

作者单位： 内蒙古科技大学包头医学院

项目金额： 47万元

中文摘要： MicroRNA是一种大小约为21～23nt的单链小分子RNA，通过转录后调控，精细调节靶基因的表达。已有研究显示miRNAs参与了高血压心肌重塑的多条信号通路。在前期研究的基础上，miR-139-5p因其在心肌重塑动物模型心肌中的显著异常表达引起了我们的关注。生物信息学预测ROCK2可能是miR-139-5p的下游靶基因。激活的Rho /ROCK 信号通路通过Caspase 依赖的凋亡途径及Bcl-2家族调节的线粒体途径促进心肌细胞凋亡。本研究拟从分子-细胞-蛋白水平揭示miR-139-5p作用于Rho /ROCK 信号通路的分子机制，从而探讨miR-139-5p通过介导细胞凋亡信号通路参与高血压心肌重塑的病理生理学机制，为将来高血压心肌重塑的治疗策略提供依据。

中文关键词： MicroRNA；信号通路；ROCK2；心肌重塑

英文摘要： MicroRNA，a class of small RNA Moleculars of 21～23 nucleotides, regulated the expression of target gene post-transcriptionally.The results of previous studies showned that miRNAs involved in the pathophysiological process of hypertensive myocardial remolding though different singal pathway.According to the previous results of our study, it raised intresting that miR-139-5p was aberrant expressed in the myocardium of 2K1C Hypertension model.Meanwhile, we found that miR-139-5p probably control the expression of ROCK2 as a target gene based on bioinformation analysis.Rho/ROCK singal pathway activated the process of cardiomyocytes apopsis by two ways: Caspase-dependent apoptotic pathway and mitochondrial apoptotic pathway regulated by Bcl-2 family. Therefore, our study aimed to reveal the molecular mechanism refers to miR-139-5p regulating Rho /ROCK singal pathway from molecular to cell to protein levels by steps, and then to explain the mechanism of miR-139-5p involved in the pathophysiological process of hypertensive myocardial remolding mediated by apoptosis pathway.The results of our study may provide a therapeutic strategy for the treatment of patients with left ventricular hypertrophy.

英文关键词： MicroRNA;Singal pathway;ROCK2;Cardiac remodeling