调控诱导肝星状细胞（HSCs）活化的信号通路是逆转肝纤维化的重要策略。过表达小窝蛋白-1（Caveolin-1）抑制蛋白酶激活受体2（PAR-2）介导的HSCs活化，但其调控机制尚不清楚。我们前期发现Caveolin-1与PAR-2在HSCs存在蛋白相互作用。因此，提出“Caveolin-1通过负调控PAR-2信号通路抑制HSCs激活”假说。本项目拟通过HSCs体外培养，利用RNA干扰和蛋白过表达技术抑制和增强Caveolin-1表达，观察HSCs活化和相关信号分子表达的变化，并筛选Caveolin-1的互作分子，揭示Caveolin-1负调控PAR-2信号转导的机制；通过肝纤维化小鼠模型，利用腺病毒转染技术使其表达Caveolin-1，证实过表达Caveolin-1阻断肝纤维化的形成。研究结果将进一步阐明PAR-2信号通路的活化调控机制，同时为寻找逆转或阻断肝纤维化的靶点分子提供新思路。

Regulation of signaling pathways that mediated hepatic stellate cells (HSCs) activation is one of the important strategy for anti-hepaticfibrosis treatment. Overexpression of Caveolin-1 inhibited PAR-2 mediated HSCs activation, but the mechanism is unclear. We found Caveolin-1and PAR-2 could interact with each other in HSCs in previous study. So, we propose that Caveolin-1 inhibits HSCs activation through blocking PAR-2 signaling pathways. The project will reveal the mechanism that Caveolin-1 inhibits HSCs activation through negative regulating PAR-2 signaling pathways by RNA interference and overexpression of Caveolin-1 to investigate the change of HSCs activation, the expression of related signal molecule and the molecule that interact with Caveolin-1 based on HSCs culture. Furthermore, we will confirm that Caveolin-1 reduces the formation of hepatic fibrosis in mice transfected with Ad-Caveolin-1. The study results will further clarify the regulating mechanism of PAR-2 signaling on HSCs activation, also provide new insight into finding of the new target to reverse or block hepatic fibrosis.