SDC-4对晶状体上皮细胞TGF/Notch信号通路及上皮间质转化的调控作用

我们前期研究发现多配体蛋白聚糖（SDC-4）参与了成纤维生长因子（FGF）通路中PKCα/Akt、ERK信号途径和整合素通路中FAK的激活，抑制SDC-4的表达可以抑制晶状体上皮细胞（LECs）的增殖、粘附。近期我们发现SDC-4基因敲除可以抑制转化生长因子（TGF）下游Smad2的磷酸化激活及Notch受体的表达，进而抑制LECs的上皮间质转化（EMT）。因此我们推测：SDC-4可以同时抑制FGF、整合素以及TGF三条的信号通路，而且可以阻断相邻细胞间Notch信号的传导从而抑制后发性白内障的形成。本项目拟：1）SDC-4基因敲除/过表达对TGF诱导的LECs的EMT的影响2）蛋白组学定量分析SDC-4调控TGF-β/Notch信号通路中的关键信号分子3）构建外伤诱导小鼠前囊下白内障模型，同时取组织进行单细胞测序，从体内实验进一步验证，以期为后发性白内障的预防和治疗提供新的靶点。

In our previous study, we found that SDC-4 was involved in the activation of PKC /Akt, ERK and FAK in the fibroblast growth factor (FGF) and integrin signaling pathway, which result in inhibition of the proliferation and adhesion of LECs via SDC-4 suppression. Recently, we found that downregulation of SDC-4 inhibited transforming growth factor (TGF) and the expression of Notch receptor through the blockade of Smad2 activation, thus suppressing epithelial mesenchymal transformation (EMT). It was speculated that SDC-4 could simultaneously inhibit the signaling pathways of FGF, integrin and TGF, as well as block the Notch signaling, thereby inhibiting the formation of posterior capsular opacification. In this project we aim to study the pathogenesis of EMT through targeting SDC-4. We analyze the TGF induced EMT of LECs after knock out or over expression of SDC-4 gene. We will probe into the key signaling molecules in the SDC-4/TGF-β/Notch signaling pathway via quantitative analysis of proteomics. Moreover, we will establish injury-induced anterior subcapsular cataract models of mouse and observe the influences of SDC-4 on cataract formation using single-cell RNA sequencing. The purpose of this project is to explore a new target in the prevention and treatment of posterior capsule opacification.