Yang Yoon Mee, Seki Ekihiro
Department of Medicine, Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Curr Pathobiol Rep. 2015 Dec;3(4):253-261. doi: 10.1007/s40139-015-0093-z. Epub 2015 Sep 30.
Hepatocyte death, inflammation, and liver fibrosis are the hallmarks of chronic liver disease. Tumor necrosis factor-α (TNFα) is an inflammatory cytokine involved in liver inflammation and sustained liver inflammation leads to liver fibrosis. TNFα exerts inflammation, proliferation, and apoptosis. However, the role of TNFα signaling in liver fibrosis is not fully understood. This review highlights the recent findings demonstrating the molecular mechanisms of TNFα and its downstream signaling in liver fibrosis. During the progression of liver fibrosis, hepatic stellate cells play a pivotal role in a dynamic process of production of extracellular matrix proteins and modulation of immune response. Hepatic stellate cells transdifferentiate into activated myofibroblasts in response to damaged hepatocyte-derived mediators and immune cell-derived cytokines/chemokines. Here, we will discuss the role of TNFα in hepatic stellate cell survival and activation and the crosstalk between hepatic stellate cells and hepatocytes or other immune cells, such as macrophages, dendritic cells, and B cells in the development of liver fibrosis.
肝细胞死亡、炎症和肝纤维化是慢性肝病的标志。肿瘤坏死因子-α（TNFα）是一种参与肝脏炎症的炎性细胞因子，持续的肝脏炎症会导致肝纤维化。TNFα具有促炎、增殖和凋亡作用。然而，TNFα信号通路在肝纤维化中的作用尚未完全明确。本综述重点介绍了近期有关TNFα及其下游信号通路在肝纤维化中的分子机制的研究发现。在肝纤维化进展过程中，肝星状细胞在细胞外基质蛋白产生和免疫反应调节的动态过程中起关键作用。肝星状细胞会响应受损肝细胞衍生的介质以及免疫细胞衍生的细胞因子/趋化因子而转分化为活化的肌成纤维细胞。在此，我们将讨论TNFα在肝星状细胞存活和激活中的作用，以及肝星状细胞与肝细胞或其他免疫细胞（如巨噬细胞、树突状细胞和B细胞）在肝纤维化发生发展过程中的相互作用。
