Lang A, Brenner D A
University of North Carolina at Chapel Hill, Department of Medicine, Chapel Hill, USA.
Ital J Gastroenterol Hepatol. 1999 Mar;31(2):173-9.
Hepatic stellate cells are now recognized as the major source of extracellular matrix in hepatic fibrosis. Following liver injury the hepatic stellate cell changes from a quiescent to an activated cell. The activation process includes an increased proliferation rate, a phenotypic change to a myofibroblast-like cell, loss of vitamin A stores, increased extra-cellular matrix protein synthesis and contractility. Furthermore, hepatic stellate cells have been implicated in hepatic inflammation through their ability to secrete cytokines and chemokines. Here, we review the literature on the molecular pathogenesis of hepatic stellate cells activation with emphasis on the most recent findings. The reviewed topics include transcriptional and post-transcriptional regulation of the genes encoding type I collagen in hepatic stellate cells; the role of the transcription factor nuclear factor Kappa B in the hepatic stellate cell activation; focal adhesion kinase and integrin-mediated signal transduction in hepatic stellate cell, and apoptosis in hepatic stellate cells. New insight into hepatic stellate cell activation and death may lead to the development of novel therapies for hepatic fibrosis.
肝星状细胞现在被认为是肝纤维化中细胞外基质的主要来源。肝损伤后，肝星状细胞从静止细胞转变为活化细胞。激活过程包括增殖率增加、向肌成纤维细胞样细胞的表型转变、维生素A储存的丧失、细胞外基质蛋白合成增加和收缩性增强。此外，肝星状细胞通过分泌细胞因子和趋化因子参与肝脏炎症。在这里，我们回顾了关于肝星状细胞激活分子发病机制的文献，重点是最新发现。回顾的主题包括肝星状细胞中编码I型胶原基因的转录和转录后调控；转录因子核因子κB在肝星状细胞激活中的作用；肝星状细胞中的粘着斑激酶和整合素介导的信号转导，以及肝星状细胞中的凋亡。对肝星状细胞激活和死亡的新见解可能会导致开发治疗肝纤维化的新疗法。
