University of Torino, Dept. Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, Corso Raffaello 30, 10125 Torino, Italy.
University of Torino, Dept. Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, Corso Raffaello 30, 10125 Torino, Italy.
Arch Biochem Biophys. 2014 Apr 15;548:20-37. doi: 10.1016/j.abb.2014.02.015. Epub 2014 Mar 11.
Liver fibrogenesis is a dynamic and highly integrated molecular, tissue and cellular process, potentially reversible, that drives the progression of chronic liver diseases (CLD) towards liver cirrhosis and hepatic failure. Hepatic myofibroblasts (MFs), the pro-fibrogenic effector cells, originate mainly from activation of hepatic stellate cells and portal fibroblasts being characterized by a proliferative and survival attitude. MFs also contract in response to vasoactive agents, sustain angiogenesis and recruit and modulate activity of cells of innate or adaptive immunity. Chronic activation of wound healing and oxidative stress as well as derangement of epithelial-mesenchymal interactions are "major" pro-fibrogenic mechanisms, whatever the etiology. However, literature has outlined a complex network of pro-fibrogenic factors and mediators proposed to modulate CLD progression, with some of them being at present highly debated in the field, including the role of epithelial to mesenchymal transition and Hedgehog signaling pathways. Hypoxia and angiogenesis as well as inflammasomes are recently emerged as ubiquitous pro-inflammatory and pro-fibrogenic determinants whereas adipokines are mostly involved in CLD related to metabolic disturbances (metabolic syndrome and/or obesity and type 2 diabetes). Finally, autophagy as well as natural killer and natural killer-T cells have been recently proposed to significantly affect fibrogenic CLD progression.
肝纤维化是一个动态的、高度整合的分子、组织和细胞过程，具有潜在的可逆性，它促使慢性肝病（CLD）向肝硬化和肝衰竭发展。肝肌成纤维细胞（MFs）是促纤维化的效应细胞，主要来源于肝星状细胞和门脉成纤维细胞的激活，其特征是增殖和存活的态度。MFs 还会对血管活性物质收缩，维持血管生成，并招募和调节固有或适应性免疫细胞的活性。慢性激活的伤口愈合和氧化应激以及上皮-间充质相互作用的紊乱是“主要”的促纤维化机制，无论病因如何。然而，文献已经概述了一个复杂的促纤维化因素和介质网络，这些因素和介质被认为可以调节 CLD 的进展，其中一些在该领域目前存在很大争议，包括上皮-间充质转化和 Hedgehog 信号通路的作用。缺氧和血管生成以及炎症小体最近被认为是普遍的促炎和促纤维化决定因素，而脂肪因子主要参与与代谢紊乱（代谢综合征和/或肥胖症和 2 型糖尿病）相关的 CLD。最后，自噬以及自然杀伤和自然杀伤 T 细胞最近被提出可以显著影响纤维化 CLD 的进展。
