Mig-6/EGFR信号通路在砷致肝纤维化损伤中的作用及其机制研究

地方性砷中毒是严重危害人类健康的地方病之一，除了能够导致皮肤损伤之外，长期砷暴露还能够导致不同程度的肝纤维化损伤，但其具体机制目前尚不清楚。最近研究显示丝裂原诱导基因6（Mig-6）/表皮生长因子受体（EGFR）信号通路及上皮间-质转化（epithelial-mesenchymal transition, EMT）在各种因素导致的纤维化损伤过程中均发挥重要作用。然而，Mig-6/EGFR信号通路是否参与砷致肝纤维化损伤以及其是否能够通过EMT途径参与该过程，这一系列科学问题目前均未明确。本项目拟在以往的研究基础上，结合砷毒性机制研究新进展，通过人群、动物及细胞三个层面运用流行病学、分子生物学、表观遗传学等研究手段系统探讨Mig-6/EGFR信号通路在砷致肝纤维化发生发展过程中的作用及其调控机制，为砷中毒肝损伤的防治提供新的思路和策略。

Endemic arsenicosis is one of the most harmful endemic disease, in addition to cause several types of skin lesions, in recent years our group and other researches also found that long-term exposure to arsenic can lead to various degree of liver fibrosis, but the underlying mechanisms remain obscure. Recent studies suggested that Mig-6/EGFR signaling pathway and epithelial-mesenchymal transition (EMT) appear to play important roles in fibrosis caused by various factors. However, it is unclear whether or not Mig-6/EGFR signaling pathway is involved in arsenic-induced liver fibrosis via EMT pathway. In the present project, on the basis of our previous study, we will investigate the role and the molecular mechanisms of Mig-6/EGFR signaling pathway in arsenic-induced liver fibrosis through both in vivo and in vitro studies. This project is likely to provide a new approach for scientific prevention and control of arsenic-induced liver injury.