TGF-βsmads信号通路对失神经骨骼肌纤维化调控机制的实验研究

项目名称： TGF-βsmads信号通路对失神经骨骼肌纤维化调控机制的实验研究

项目编号： No.30872627

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 陈振兵

作者单位： 华中科技大学

项目金额： 26万元

中文摘要： 如何提高周围神经损伤修复后的疗效是目前临床和实验亟待解决的问题，神经损伤后失神经骨骼肌发生纤维化，影响神经修复后的疗效，但其发生机制尚不清楚。最近研究表明TGF-βsmads 信号通路在调控肝、肾纤维化启动过程中发挥重要作用。本课题以在肝、肾纤维化启动过程中起关键调控作用的Smads 蛋白为切入点，研究Smads蛋白在TGF-β#33268;失神经骨骼肌纤维化过程中的调控作用。本课题拟构建smad7的逆转录病毒载体和smad3的siRNA，转染到体外培养的失神经MDSC，通过促进smad7过表达和抑制smad3的表达，检测其对CTGF和细胞外基质生成的影响，在体内进一步验证smad7过表达以及阻断smad3表达对防止纤维化的效果。本课题初步阐明了TGF-βsmads 信号通路对失神经骨骼肌纤维化启动过程中的调控机制，为防止失神经骨骼肌纤维化，提高神经修复后的疗效提供新的研究方向和理论依据。

中文关键词： 转化生长因子；smads；纤维化；失神经骨骼肌

英文摘要： How to improve the curative effect of peripheral nervous regeneration is a pressing task needed to be solved both clinically and scientifically. The skeletal muscular fibrosis following denervation directly influences the prognosis of nervous regeneration. The specific mechanism of muscular fibrosis remains unclear. Recent researches have suggested that TGFβsmad3 signal transduction pathway is the key point to initiate the process of hepatic and nephritic fibrosis. To investigate the regulatory function of Smads protein in the process of denervated myofibrosis ,this project has construct a retrovirus vector carried with Smad7 and plasmid which contains small interfering RNAs (siRNAs) sequence against Smad3, transfect them into the Muscle-derived stem cell(MDSC)of denervated skeletal muscle in vitro. Promoting the expression of Smad7 and inhibition the expression of Smad3 can regulate the downstream production of connective tissue growth factor(CTGF)and extracelluar matrix. This also further confirms the absolute effect for the inhibition of skeletal muscular fibrosis.The project initially elucidates the regulatory mechanism of TGFβsmad3 signal transduction pathway in setting up the process of skeletal muscular fibrosis, provides a new research orientation and theory evidence on preventing skeletal muscle from fibrosis.

英文关键词： Transforming growth factor-βsmads;fibrosis;denervated skeletal muscle