Brady L M, Beno D W, Davis B H
Department of Medicine, University of Chicago, IL, USA.
Biochem J. 1996 Jun 15;316 ( Pt 3)(Pt 3):765-9. doi: 10.1042/bj3160765.
Hepatic stellate cells are exposed to elevated bile acid levels during hepatic injury and fibrogenesis. Upon activation, the stellate cell becomes a major effector cell during the development of hepatic fibrosis and cirrhosis. Bile acids may function as costimulatory signalling molecules. This hypothesis was tested in vitro using rat-derived hepatic stellate cells. Bile acids were studied at concentrations that occur during cirrhosis in vivo. Conjugated and unconjugated bile acids rapidly induced egr and fos gene expression as well as cytoplasmic mitogen-activated protein kinase (MAPK) activation. Protein kinase C was required for both egr induction and MAPK activation. These studies imply that bile acids could contribute to the perpetuation of hepatic fibrosis by helping to keep the stellate cell in an activated state.
在肝损伤和纤维化过程中，肝星状细胞会暴露于升高的胆汁酸水平。激活后，星状细胞成为肝纤维化和肝硬化发展过程中的主要效应细胞。胆汁酸可能作为共刺激信号分子发挥作用。该假说在体外使用大鼠来源的肝星状细胞进行了验证。研究了体内肝硬化时出现的胆汁酸浓度。结合型和非结合型胆汁酸迅速诱导早期生长反应基因（egr）和原癌基因fos的表达以及细胞质丝裂原活化蛋白激酶（MAPK）的激活。蛋白激酶C对于egr诱导和MAPK激活均是必需的。这些研究表明，胆汁酸可能通过帮助使星状细胞维持在激活状态而促进肝纤维化的持续发展。
