Department of Molecular Medicine, University of Padua, Padua, Italy.
Liver Center, Department of Medicine, Yale University, New Haven, Connecticut.
Semin Liver Dis. 2020 Aug;40(3):282-297. doi: 10.1055/s-0040-1705109. Epub 2020 Mar 11.
The extracellular matrix is a highly reactive scaffold formed by a wide array of multifunctional molecules, encompassing collagens and noncollagenous glycoproteins, proteoglycans, glycosaminoglycans, and polysaccharides. Besides outlining the tissue borders, the extracellular matrix profoundly regulates the behavior of resident cells by transducing mechanical signals, and by integrating multiple cues derived from the microenvironment. Evidence is mounting that changes in the biostructure of the extracellular matrix are instrumental for biliary repair. Following biliary damage and eventually, malignant transformation, the extracellular matrix undergoes several quantitative and qualitative modifications, which direct interactions among hepatic progenitor cells, reactive ductular cells, activated myofibroblasts and macrophages, to generate the ductular reaction. Herein, we will give an overview of the main molecular factors contributing to extracellular matrix remodeling in cholangiopathies. Then, we will discuss the structural alterations in terms of biochemical composition and physical stiffness featuring the "desmoplastic matrix" of cholangiocarcinoma along with their pro-oncogenic effects.
细胞外基质是一种由多种多功能分子形成的高度反应性支架，包括胶原和非胶原糖蛋白、蛋白聚糖、糖胺聚糖和多糖。除了勾勒出组织边界外，细胞外基质还通过传递机械信号，以及整合来自微环境的多种信号，深刻地调节常驻细胞的行为。越来越多的证据表明，细胞外基质的生物结构变化对胆管修复至关重要。在胆管损伤后，最终发生恶性转化后，细胞外基质经历了几种数量和质量上的改变，这些改变指导肝祖细胞、反应性胆管细胞、激活的肌成纤维细胞和巨噬细胞之间的相互作用，从而产生胆管反应。在此，我们将概述导致胆管疾病中细胞外基质重塑的主要分子因素。然后，我们将讨论“纤维母细胞性基质”的生化组成和物理硬度方面的结构改变及其致癌作用。
