Hippo信号通路在肝纤维化过程中的调控机制研究进展  

Research Progress in Regulatory Mechanism of Hippo Signaling Pathway in Liver Fibrosis Process

作　　者：陈娇娇 周莹群 CHEN Jiaojiao;ZHOU Yingqun(School of Clinical Medicine,Shanghai Tenth Hospital,Nanjing Medical University,Shanghai 200072,China;Department of Gastroenterology,Shanghai Fourth People′s Hospital,Shanghai 200434,China;Department of Gastroenterology,Shanghai Tenth People′s Hospital,Shanghai 200072,China)

机构地区：[1]南京医科大学上海十院临床医学院,上海200072 [2]上海市第四人民医院消化内科,上海200434 [3]上海市第十人民医院消化内科,上海200072

出　　处：《医学综述》2023年第14期2717-2722,共6页Medical Recapitulate

基　　金：上海市科学技术委员会科研计划项目(19ZR1439900)。

摘　　要：肝纤维化是肝脏慢性损伤的一种修复反应,其特征为肝脏中细胞外基质的过量沉积,肝星状细胞(HSC)的激活是肝纤维化发生的中心环节。Hippo信号通路是一条高度保守的信号通路,其参与了哺乳动物多种细胞和器官的稳态调控,且能够通过调控多种细胞、趋化因子、分子信号等相互作用参与肝纤维化的发生发展。Hippo信号通路能够参与HSC的激活,其下游转录激活因子Yes相关蛋白(YAP)和含PDZ结合基序的转录共激活因子(TAZ)是HSC激活的关键调节因子。YAP/TAZ在肝纤维化过程中表达上调,并表现出广泛的核累积,抑制YAP/TAZ能有效改善肝纤维化的发生发展。因此,深入研究Hippo信号通路与肝纤维化的关系可以为肝纤维化患者的治疗提供新靶点。Liver fibrosis is a repair response to chronic liver injury characterized by excessive deposition of extracellular matrix in the liver,and activation of hepatic stellate cells(HSC)is a central part of the development of liver fibrosis.The Hippo signaling pathway is a highly conserved signaling pathway involved in the regulation of homeostasis in a variety of mammalian cells and organs,and is able to regulate the interaction of multiple cells,chemokines,and molecular signals to participate in the development of liver fibrosis.The Hippo signaling pathway is involved in HSC activation,and its downstream transcriptional activator Yes-associated protein(YAP)and transcriptional co-activator with PDZ binding motif(TAZ)are key regulators of HSC activation.YAP/TAZ expression is upregulated during liver fibrosis and exhibits extensive nuclear accumulation,and inhibition of YAP/TAZ is effective in improving the development of liver fibrosis.Therefore,an in-depth study of the relationship between the Hippo signaling pathway and liver fibrosis can provide new targets for the treatment of liver fibrosis patients.

关 键 词：肝纤维化 肝星状细胞 Hippo信号通路 Yes相关蛋白/含PDZ结合基序的转录共激活因子 

分 类 号：R575.2[医药卫生—消化系统]