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基质金属蛋白酶在肝损伤和纤维化中的作用。

Matrix metalloproteinase functions in hepatic injury and fibrosis.

机构信息

Department of Gastroenterology, Justus-Liebig-University Giessen, Gaffkystr. 11c, D-35392 Giessen, Germany.

出版信息

Matrix Biol. 2018 Aug;68-69:452-462. doi: 10.1016/j.matbio.2017.11.011. Epub 2017 Dec 6.

Abstract

Liver fibrosis is the most common final outcome for chronic liver diseases. The complex pathogenesis includes hepatic parenchymal damage as a result of a persistent noxe, activation and recruitment of immune cells, activation of hepatic stellate cells, and the synthesis of fibrotic extracellular matrix (ECM) components leading to scar formation. Clinical studies and animal models demonstrated that fibrosis can be reversible. In this regard matrix metalloproteinases (MMPs) have been focused as therapeutic targets due to their ability to modulate tissue turnover during fibrogenesis as well as regeneration and, of special interest, due to their influence on cellular behavior like proliferation, gene expression, and apoptosis that, in turn, impact fibrosis and regeneration. The current review aims to summarize and update the knowledge about expression pattern and the central roles of MMPs in hepatic fibrosis.

摘要

肝纤维化是慢性肝病最常见的终末结果。其复杂的发病机制包括:持续性毒物导致的肝实质损伤、免疫细胞的激活和募集、肝星状细胞的激活以及纤维细胞外基质(ECM)成分的合成,导致疤痕形成。临床研究和动物模型表明,纤维化是可以逆转的。在这方面,基质金属蛋白酶(MMPs)已被作为治疗靶点,因为它们具有在纤维化形成过程中调节组织更新以及再生的能力,特别是由于它们对细胞行为的影响,如增殖、基因表达和凋亡,这些反过来又影响纤维化和再生。本综述旨在总结和更新有关 MMP 在肝纤维化中的表达模式和核心作用的知识。

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