NLRC5介导的巨噬细胞极化对肝纤维化形成与逆转的调控及机制研究

项目名称： NLRC5介导的巨噬细胞极化对肝纤维化形成与逆转的调控及机制研究

项目编号： No.81473268

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李俊

作者单位： 安徽医科大学

项目金额： 100万元

中文摘要： KC在肝纤维化形成与逆转过程中具有重要作用。肝纤维化形成期KC分泌炎症因子诱导HSC活化增殖，逆转期KC可抑制NF-κB信号通路诱导HSC凋亡。有报道肝脏损伤与肝外募集巨噬细胞密切相关，亦有研究表明组织固有巨噬细胞原位快速增殖，是导致炎症作用的主要原因。在肝纤维化不同时期，KC功能变化是否与其不同来源有关？巨噬细胞存在极化现象，在肝纤维化不同时期，KC功能变化是否与其极化表型不同相关？调控机制如何？课题组研究证实，NLRC5(NOD蛋白家族，负性调控NF-κB等信号通路)，调控巨噬细胞极化，在肝纤维化形成与逆转过程中表达发生变化，NLRC5是否参与肝纤维化的形成与逆转，其作用是否与调控KC极化状态有关？其变化受何种机制调控？这些科学问题均尚未阐明。课题拟围绕肝纤维化不同时期，肝脏巨噬细胞来源、极化状态，NLRC5对其可能的调控机制进行研究。为理解肝纤维化发病机制及寻找药物新靶点提供新思路。

中文关键词： 肝纤维化；巨噬细胞；细胞凋亡；NOD样受体；信号通路

英文摘要： KC plays an important role in the initiation and reversal of liver fibrosis. KC secrets inflammatory cytokines to induce the activation and proliferation of HSC in the initiation stage while enhancing HSC apoptosis through inhibiting NF-κB signaling pathway in the reversal of liver fibrosis. It is reported that recruited macrophages are closely related with the degree of liver injury,while another study indicates that resident macrophages proliferate rapidly as the main cause of inflammation. So at different stages of liver fibrosis , whether KC functional changes related to its different origins or their polarized phenotypes ? what is regulatory mechanisms? These scientific issues have not yet been fully understood. Our pilot study demonstrated that NLRC5, a member of NOD protein family , is altered in polarization of macrophages and different stage of liver fibrosis So it is interesting to determine whether NLRC5 participates in the process of liver fibrosis and whether it functions through regulating the polarization of KC ? Collectively, By focusing on several elements including different stages of liver fibrosis, different origins of liver macrophages, distinct polarization state of KCs, the function and underlying mechanisms of NLRC5 in these processes will be further explored.

英文关键词： liver fibrosis;macrophage;apoptosis;NOD-like receptors (NLRs);signal