受TGF-β/Smad4信号通路调控的miRNA在损伤骨骼肌纤维化中的功能研究

项目名称： 受TGF-β/Smad4信号通路调控的miRNA在损伤骨骼肌纤维化中的功能研究

项目编号： No.81472142

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 陈疾忤

作者单位： 复旦大学

项目金额： 72万元

中文摘要： TGF-β/Smad信号通路在骨骼肌损伤后的纤维化进程中发挥关键作用，有研究表明Smad4与miRNA的表达和成熟有密切关联，然而是否存在相关miRNA受到TGF-β/Smad信号通路调控并参与损伤骨骼肌纤维化过程尚不明确。本研究拟利用体外细胞实验对miRNA进行筛选，通过对目标miRNA的干预，检测成肌细胞纤维化程度以锁定目标miRNA；并利用骨骼肌特异性敲除Smad4小鼠的钝挫伤模型，验证目标miRNA。进一步在细胞和体内验证目标miRNA对骨骼肌纤维化的影响，进而预测靶基因并验证其功能。本项目通过探索TGF-β/Smad信号通路调控的miRNA在损伤骨骼肌纤维化中的作用，更深入地探讨损伤骨骼肌纤维化的发生机制，为探讨新的治疗途径提供思路和理论依据。

中文关键词： 骨骼肌；运动损伤；纤维化；微小RNA；TGFbeta/smad信号通路

英文摘要： It has been shown that TGF-β/Smad pathway, playing a key role in the skeletal muscle fibrosis following injury, has a strong correlation with the expression and maturation of microRNA. However, there is little evidence about the miRNA regulated by TGF-β/Smad pathway during the fibrosis process and its function on the fibrosis of injured muscle. In this study, the target miRNA will be selected by the experiment in vitro and confirmed by the animal models. To investigate the function of miRNA, we will measure the fibrosis markers in C2C12 cells and in vivo using the mouse model of skeletal muscle fibrosis. Functional analysis of miRNA on muscle fibrosis will be demonstrated both in vitro and in vivo. Additionally, the direct targets of miRNA that mediate its effects remain to be identified and characterized for therapeutic purposes. Together, we propose that the effect of the miRNA regulated by TGF-β/Smad pathway on muscle fibrosis should be explored, and the molecular mechanism of the fibrosis during muscle injury should be further investigated. It is conceivable that modulation of miRNA regulated by TGF-β signaling could be a novel therapeutic strategy in the treatment of skeletal muscle fibrosis.

英文关键词： skeletal muscle;sports injury;fibrosis;microRNA;TGFbeta/smad signal pathway