MicroRNA-139-5p调控心肌重构的分子机制

项目名称： MicroRNA-139-5p调控心肌重构的分子机制

项目编号： No.81500236

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 苏明

作者单位： 中国医学科学院阜外医院

项目金额： 18万元

中文摘要： MicroRNA是心肌重构的重要调控因子，目前仍有众多microRNA的功能有待揭示。我们的前期结果发现miR-139-5p在患者肥厚心肌组织中表达下调，体外敲低miR-139-5p导致心肌细胞肥大，提示miR-139-5p是新的心肌重构调控因子。本课题将1）以乳鼠心肌细胞为体外模型，分别在基线及病理状态下，通过改变细胞内miR-139-5p的表达水平，检测miR-139-5p对靶蛋白及相关通路的影响，揭示miR-139-5p对心肌细胞肥大的调控作用及机制；2）以心肌特异性miR-139-5p转基因小鼠为动物模型，通过超声心动图、病理组织学等方法，检测基线状态和压力负荷下，miR-139-5p在体内对心肌重构的调控作用，并探讨以miR-139-5p作为靶点干预心肌重构的可行性。通过本课题，我们将揭示miR-139-5p对心肌重构的调控作用和机制，并为心肌重构的治疗提供新的潜在靶点。

中文关键词： 心肌重构；微小RNA

英文摘要： MicroRNAs play important roles in regulating cardiac remodeling. Previously, we identified that the expression of miR-139-5p was down-regulated in the left ventricular tissues of hypertrophic cardiomyopathy patients. Knockdown of miR-139-5p in cardiomyocytes resulted in the enlargement of cardiomyocytes. To reveal the role of miR-139-5p in cardiac remodeling, we designed the following in vitro and in vivo studies: 1) we will overexpress or knock down miR-139-5p and detect the expression of target genes as well as the related signaling pathways in cardiomyocytes to explore the effects and mechanisms of miR-139-5p on cardiac hypertrophy; 2) we will construct cardiac-specific miR-139-5p transgenic mouse line to evaluate the effects and mechanisms of miR-139-5p on cardiac remodeling in vivo by using echocardiography and histological assays. This study will reveal the important roles of miR-139-5p on cardiac remodeling. More importantly, our research will provide novel therapeutic targets for cardiac remodeling.

英文关键词： cardiac remodeling;microRNA