c-ski对RPE细胞EMT信号调控及其在PVR治疗中的价值

项目名称： c-ski对RPE细胞EMT信号调控及其在PVR治疗中的价值

项目编号： No.81200711

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 郭斌

作者单位： 中国人民解放军第八一医院

项目金额： 23万元

中文摘要： 视网膜色素上皮(RPE)细胞发生上皮向间质转化(EMT)是增生性玻璃体视网膜病变(PVR)发生进展的重要环节，c-ski是TGF-β等通路中重要调节分子，可调控EMT及后续过程：纤维化、胶原分泌及增生膜收缩，这可能对PVR治疗有重要意义。我们构思对RPE细胞内c-ski调控，减少细胞外基质和应力骨架蛋白合成，抑制细胞转化、迁移、胶原分泌和增生膜收缩。本课题拟在EMT组织模型和PVR动物模型研究，分析c-ski调控与EMT相关性：对临床和动物模型中组织病理检测明确它在PVR发生发展中的变化；利用构建质粒、蛋白电泳、RT-PCR、基因芯片等方法，分析c-ski高表达和抑制后RPE细胞基质分泌、纤维化及其他EMT相关过程的分子群表达变化；通过质粒转染活体视网膜，观察受转染眼PVR发生进展过程及相关分子群表达变化。探讨c-ski调节RPE细胞EMT的分子机制，可为治疗PVR提供一个新的研究思路。

中文关键词： 视网膜色素上皮；上皮间质转化；增生性玻璃体视网膜病变；转化生长因子；c-ski

英文摘要： The changes of retinal pigment epithelium (RPE) cells resulting from an epithelial-mesenchymal transition (EMT) play key roles in proliferative vitreoretinopathy (PVR), which leads to complex retinal fibrotic disorder and the loss of vision. Many mechanisms have been described, by which c-Ski regulates essential signaling pathways, e.g., the TGF-β pathway and exists in regulating EMT and the following process: fibrosis, collagen secretion, membrane formation and traction. So it is speculated that the regulatory function of c-ski may be helpful to treat PVR. We conceive regulating expression of c-ski to reduce extracellular matrix and stress skeleton protein synthesis and to inhibit RPE cell proliferation, migration, secretion, fibrotic membrane formation and traction. The correlation between the expression of c-ski and EMT will be observed in EMT tissue model and PVR animal model, and the change of c-ski expression in the development and progression of PVR will both be studied in the clinical and animal specimens by histopathologic examination. The effect of c-ski expression in RPE cells on extracellular matrix, fibrosis and other EMT molecules will be observed by constructing plasmid, protein electrophoresis, RT-PCR and gene chip, et al. The changes of PVR development and relevant molecules will be studied in t

英文关键词： retinal pigment epithelium；epithelial-mesenchymal transition；proliferative vitreoretinopathy；transforming growth factor；c-ski