Khurana Amit, Sayed Nilofer, Allawadhi Prince, Weiskirchen Ralf
Center for Biomedical Engineering (CBME), Indian Institute of Technology (IIT), Hauz Khas, New Delhi, India.
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, Aachen, Germany.
Ann Transl Med. 2021 Apr;9(8):728. doi: 10.21037/atm-20-2948.
Liver fibrosis is one of the leading complications of a variety of chronic liver disorders, including the nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, liver cirrhosis and liver failure. The progression of liver fibrosis is driven by chronic inflammation, which activates the secretory fibroblasts to the myofibroblast phenotype. These specialized liver cells are called as hepatic stellate cells (HSCs). The excessive extracellular matrix (ECM) secretion creates a large number of complications. Fibrosis is the result of imbalance between the matrix synthesizing and matrix degrading factors. The major ECM proteins include the matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), lysyl oxidases (LOX), lysyl oxidase-like (LOXLs) enzymes, tenascins and others. These ECM proteins present novel avenues for the therapeutics of liver fibrosis. The current review highlights the major role played by these critical matrix proteins in liver fibrosis. Further, some of the targeted formulations used against these proteins are discussed and suggestions are provided to select the course of research for successful clinical translation of basic research findings for the amelioration of liver fibrosis.
肝纤维化是多种慢性肝脏疾病的主要并发症之一，包括非酒精性脂肪性肝病、非酒精性脂肪性肝炎、肝硬化和肝衰竭。肝纤维化的进展由慢性炎症驱动，慢性炎症会使分泌性成纤维细胞转变为肌成纤维细胞表型。这些特殊的肝细胞被称为肝星状细胞（HSCs）。细胞外基质（ECM）的过度分泌会引发大量并发症。纤维化是基质合成因子与基质降解因子失衡的结果。主要的ECM蛋白包括基质金属蛋白酶（MMPs）、金属蛋白酶组织抑制剂（TIMPs）、赖氨酰氧化酶（LOX）、赖氨酰氧化酶样（LOXLs）酶、腱生蛋白等。这些ECM蛋白为肝纤维化的治疗提供了新途径。本综述重点介绍了这些关键基质蛋白在肝纤维化中所起的主要作用。此外，还讨论了针对这些蛋白的一些靶向制剂，并就如何选择研究方向以成功地将基础研究成果临床转化用于改善肝纤维化提供了建议。
