Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets.
Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets.
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DOI：
10.3748/wjg.v22.i48.10512
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发表时间：
2016-12-28
影响因子：
4.3
通讯作者：
Wang CX
中科院分区：
文献类型：
--
作者：
Zhang CY;Yuan WG;He P;Lei JH;Wang CX
肝纤维化是一个可逆的伤口愈合过程，旨在维持器官的完整性，并作为肝硬化的关键前期阶段，在没有肝移植的情况下，最终将进展为肝细胞癌。肝纤维化通常是由各种因素引起的慢性肝损伤引起的，主要是病毒感染、血吸虫病和酒精中毒;然而，确切的病理机制仍不清楚。尽管许多药物已在体外和动物模型中显示具有抗纤维化活性，但这些药物中没有一种在临床上显示有效。重要的是，肝星状细胞（HSC）通过分泌促进门静脉纤维细胞、成纤维细胞和骨髓源性肌成纤维细胞产生胶原并由此传播纤维化的纤维化因子，在肝纤维化的起始、进展和消退中发挥关键作用。这些细胞会与相邻细胞发生复杂的串扰，导致疤痕和随后的肝损伤。因此，了解肝纤维化的分子机制及其与HSC的关系对于发现新的治疗靶点至关重要。这篇综述概述了HSC在肝纤维化中的作用，并详细介绍了抑制HSC活性的新策略，从而为肝纤维化的潜在治疗提供了新的见解。
Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells (HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.
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影响因子：
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