Department of Pharmacy, The People's Hospital of Bozhou, Bozhou, 236800, China.
Inflamm Res. 2015 Jan;64(1):1-7. doi: 10.1007/s00011-014-0772-y. Epub 2014 Oct 7.
The objective of the review is to examine the crossroads of autophagy, inflammation, and apoptosis signaling pathways and their participation in liver fibrosis.
Endoplasmic reticulum (ER) stress was emerged as a common feature relevant to the pathogenesis of diseases associated with organ fibrosis. However, the functional consequences of these alterations on ER stress and the possible involvement in liver fibrosis were currently largely unexplored. Here, we will survey the recent literature in the field and discuss recent insights focusing on some cellular models expressing mutant proteins involved in liver fibrosis.
A computer-based online search with PubMed, Scopus and Web of Science databases was performed for articles published, concerning ER stress, adaptation, inflammation and apoptosis with relevance to liver fibrosis.
Progression of liver fibrosis requires sustained inflammation leading to hepatocytes apoptosis through ER stress, whereas associated with activation of hepatic stellate cells (HSCs) into a fibrogenic and proliferative cell type. Faced with persistent and massive ER stress, HSCs adaptation starts to fail and apoptosis occurs in reversal of liver fibrosis, possibly mediated through calcium perturbations, unfolded protein response, and the pro-apoptotic transcription factor CHOP. Although limited in scope, current studies underscored that ER stress is tightly linked to adaptation, inflammation and apoptosis, and recent evidences suggested that these processes are related to the pathogenesis of liver fibrosis and its recovery.
本次综述旨在探讨自噬、炎症和细胞凋亡信号通路的交汇点及其在肝纤维化中的作用。
内质网（ER）应激被认为是与器官纤维化相关疾病发病机制相关的共同特征。然而，这些改变对 ER 应激的功能后果及其在肝纤维化中的可能参与目前在很大程度上尚未得到探索。在这里，我们将调查该领域的最新文献，并讨论最近的研究进展，重点介绍一些表达与肝纤维化相关突变蛋白的细胞模型。
使用 PubMed、Scopus 和 Web of Science 数据库进行了基于计算机的在线搜索，检索了与 ER 应激、适应、炎症和凋亡与肝纤维化相关的文章。
肝纤维化的进展需要持续的炎症，通过 ER 应激导致肝细胞凋亡，而与肝星状细胞（HSCs）激活为纤维生成和增殖细胞类型有关。面对持续和大量的 ER 应激，HSCs 的适应开始失败，细胞凋亡发生逆转肝纤维化，可能通过钙波动、未折叠蛋白反应和促凋亡转录因子 CHOP 介导。尽管研究范围有限，但目前的研究强调 ER 应激与适应、炎症和细胞凋亡密切相关，最近的证据表明这些过程与肝纤维化的发病机制及其恢复有关。
