Koyama Yukinori, Xu Jun, Liu Xiao, Brenner David A
School of Medicine, University of California, La Jolla, San Diego, Calif., USA.
Dig Dis. 2016;34(5):589-96. doi: 10.1159/000445269. Epub 2016 Jun 22.
Liver fibrosis results from many chronic injuries and often progresses to cirrhosis, liver failure, portal hypertension, and hepatocellular carcinoma. Liver transplantation is the only treatment available for patients with advanced stages of liver fibrosis. Therefore, new strategies for anti-fibrotic therapy are required. Various kinds of hepatocyte damage result in inflammation, which leads to the activation of hepatic stellate cells (HSCs), which are the major source of myofibroblasts in the liver. Myofibroblasts proliferate in response to various kinds of cytokines, chemokines, and growth factors and produce extracellular matrix proteins, which forms the fibrous scar. Myofibroblasts undergo apoptosis and inactivation when the underlying causative etiologies are cleared. Here we describe our current knowledge of targeting the steps in HSC activation as therapeutic target for liver fibrosis.
肝纤维化由多种慢性损伤引起,常进展为肝硬化、肝衰竭、门静脉高压和肝细胞癌。肝移植是肝纤维化晚期患者唯一可用的治疗方法。因此,需要新的抗纤维化治疗策略。各种肝细胞损伤会导致炎症,进而导致肝星状细胞(HSCs)活化,肝星状细胞是肝脏中肌成纤维细胞的主要来源。肌成纤维细胞会对各种细胞因子、趋化因子和生长因子产生反应而增殖,并产生细胞外基质蛋白,从而形成纤维瘢痕。当潜在的致病病因被清除时,肌成纤维细胞会发生凋亡并失活。在此,我们描述了目前关于将肝星状细胞活化步骤作为肝纤维化治疗靶点的认识。