Molecular pathogenesis of hepatic fibrosis and current therapeutic approaches.
Molecular pathogenesis of hepatic fibrosis and current therapeutic approaches.
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DOI：
10.1016/j.cbi.2011.07.001
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发表时间：
2011-09-30
影响因子：
5.1
通讯作者：
Nieto, Natalia
中科院分区：
文献类型：
--
作者：
Mormone, Elisabetta;George, Joseph;Nieto, Natalia
肝纤维化的发病机制涉及纤维胶原和其他细胞外基质蛋白的显著沉积。这是一个相当动态的伤口愈合过程，以应对由乙醇摄入、病毒感染、药物、毒素、胆汁淤积和代谢紊乱等因素引起的各种持续性肝损伤。肝纤维化改变肝脏结构，减少内皮细胞窗孔数目，导致门静脉高压。关键事件是静止的肝星状细胞活化并转化为肌纤维母细胞样细胞，随后蛋白质如α-平滑肌肌动蛋白、间质胶原、基质金属蛋白酶、金属蛋白酶组织抑制剂和蛋白聚糖上调。氧化应激是肝纤维化发病的主要因素，并且通常与抗氧化防御的降低相关。目前，对于晚期肝纤维化没有有效的治疗方法。在其早期阶段，肝纤维化在停止致病剂后是可逆的。本文就肝纤维化的病因、涉及的细胞、分子发病机制及目前的治疗方法等方面进行综述。
The pathogenesis of hepatic fibrosis involves significant deposition of fibrilar collagen and other extracellular matrix proteins. It is a rather dynamic process of wound healing in response to a variety of persistent liver injury caused by factors such as ethanol intake, viral infection, drugs, toxins, cholestasis and metabolic disorders. Liver fibrosis distorts the hepatic architecture, decreases the number of endothelial cell fenestrations and causes portal hypertension. Key events are the activation and transformation of quiescent hepatic stellate cells into myofibroblast-like cells with the subsequent up-regulation of proteins such as α-smooth muscle actin, interstitial collagens, matrix metalloproteinases, tissue inhibitor of metalloproteinases and proteoglycans. Oxidative stress is a major contributing factor to the onset of liver fibrosis and it is typically associated with a decrease in the antioxidant defense. Currently, there is no effective therapy for advanced liver fibrosis. In its early stages, liver fibrosis is reversible upon cessation of the causative agent. In this review, we discuss some aspects on the etiology of liver fibrosis, the cells involved, the molecular pathogenesis and the current therapeutic approaches.
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