摘要
多种病因引起肝脏微环境的破坏而致肝组织结构功能丧失,启动肝纤维化进程,主要以肝星状细胞(HSC)活化为肌成纤维细胞,分泌大量以胶原为主的细胞外基质(ECM)为特征表现。虽然目前对抗肝纤维化机制的研究已有很多,但仍缺乏有效的靶点药物应用于临床,近年来关于抗肝纤维化的研究多集中在肝纤维化进展期的干预,而忽略了早期肝纤维化的具体机制如何。最近关于Hippo信号在肝纤维化中的研究逐渐增多,集中于核心转录因子Yes相关蛋白(YAP)在早期活化HSC中的表达,及该通路调控HSC的状态,本文主要介绍了Hippo/YAP通路参与调控肝纤维化早期及进展期的作用,简述了调控核心因子YAP的稳定表达与核转位可逆转肝纤维化的潜在作用,表明了该通路可为临床治疗提供新的方向及靶点。
Various etiologies cause the destruction of liver microenvironment,which leads to the loss of liver structure and function and initiates the process of liver fibrosis.Hepatic stellate cells(HSCs)are mainly activated into myofibroblasts that secrete a large amount of extracellular matrix(ECM),mostly collagen.Although there have been many studies on the anti-liver fibrosis mechanism,there is still a lack of effective target drugs for clinical application,and in recent years,studies on anti-liver fibrosis have mainly focused on interventions for the advanced stage of liver fibrosis,while ignoring the specific mechanism of early-stage liver fibrosis.Recently,there have been an increasing number of studies on Hippo signaling in liver fibrosis,with a focus on the expression of the core transcription factor Yes-associated protein(YAP)in early activated HSCs and the regulation of HSC status by this pathway.This article mainly introduces the role of the Hippo/YAP pathway in the regulation of early-stage or advanced liver fibrosis and briefly describes the potential role of regulating the stable expression and nuclear translocation of the core transcription factor YAP in reversing liver fibrosis,suggesting that this pathway can provide new directions and targets for clinical treatment.
作者
赵晓璐
张春艳
高晓阳
马月宏
ZHAO Xiaolu;ZHANG Chunyan;GAO Xiaoyang;MA Yuehong(Inner Mongolia Medical University School of Basic Medicine,Hohhot 010110,China)
出处
《临床肝胆病杂志》
CAS
北大核心
2022年第7期1654-1657,共4页
Journal of Clinical Hepatology
基金
国家自然科学基金(81960759,81560706)
内蒙古自治区自然科学基金资助项目(2019MS08010,2014MS0841)
内蒙古自治区草原英才培养计划
内蒙古自治区教坛新秀培养计划
内蒙古医科大学致远人才计划项目。
