Notch信号通路在后发性白内障中的作用和机制研究

Lens epithelial cells are triggered to proliferate and undergo a transition into myofibroblasts which synthesize the contractile protein alpha smooth muscle actin (α-SMA), through a process known as epithelial to mesenchymal transition (EMT) .PCO is characterized by cellular migration onto the posterior lens capsule, deposition of aberrant amounts of extracellular matrix (ECM) andcapsular wrinkling, all of which can result in a loss of lens transparency. Notch signalling pathway has been implicated as an important contributor to epithelial to myofibroblast transformation in tumourigenesis. So We suppose Notch signaling pathway regulate α-SMA gene expression. We have certified that Notch1-receptor was highly expressed on active LECs. In this study, through in vivo animal model and in vitro cell experiments, we will confirm that Notch signaling pathway has actively effect on EMT process in LECs, and investigate the mechanism how Notch signaling pathway regulate α-SMA gene promoter.

晶状体上皮细胞（LECs）上皮-间充质转分化（EMT）是指LECs向肌成纤维细胞转变，特征性表达α-平滑肌肌动蛋白（α-SMA）的异常分化过程，是后发性白内障（PCO）主要病理改变，引起白内障术后晶状体囊膜混浊、皱缩，最终造成视力下降乃至失明。但α-SMA基因启动子的激活机制尚未明确。Notch信号通路是人体细胞间传递信息的重要途径。Notch能增强α-SMA蛋白的表达，对人体数种细胞的转分化发挥关键调控作用。基于此，我们推测Notch对LECs中的α-SMA基因的表达起着调控作用。在前期研究中，我们已证实活化的LECs出现Notch1受体的高表达。在本研究中我们将通过体外细胞和体内动物模型进一步了解Notch信号通路对LECs 发生EMT的促进作用，并在分子水平上阐明Notch信号通路对α-SMA基因启动子的调控修饰机制，进一步明确白内障术后PCO的关键机制，为其防治提供新的思路和靶点。

晶状体上皮细胞（LECs）上皮-间充质转分化（EMT）是指LECs向肌成纤维细胞转变，特征性表达α-平滑肌肌动蛋白（α-SMA）的异常分化过程，是后发性白内障（PCO）主要病理改变，引起白内障术后晶状体囊膜混浊、皱缩，最终造成视力下降乃至失明。Notch信号通路是人体细胞间传递信息的重要途径。Notch能增强α-SMA蛋白的表达，Notch对LECs中的α-SMA基因的表达起着调控作用。Jagged-1/Notch 信号通路可以激活TGFβ2诱导的EMT,并增强α-SMA的表达。同时阻断了Jagged-1/Notch 信号通路可以减缓晶状体上皮细胞的纤维化和EMT.