First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy.
First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy.
Mol Aspects Med. 2019 Feb;65:100-109. doi: 10.1016/j.mam.2018.10.003. Epub 2018 Nov 2.
Extensive tissue fibrosis is the end-stage process of a number of chronic conditions affecting the gastrointestinal tract, including inflammatory bowel disease (Crohn's disease, ulcerative colitis), ulcerative jejunoileitis, and radiation enteritis. Fibrogenesis is a physiological, reparative process that may become harmful as a consequence of the persistence of a noxious agent, after an excessive duration of the healing process. In this case, after replacement of dead or injured cells, fibrogenesis continues to substitute normal parenchymal tissue with fibrous connective tissue, leading to uncontrolled scar formation and, ultimately, permanent organ damage, loss of function, and/or strictures. Several mechanisms have been implicated in sustaining the fibrogenic process. Despite their obvious etiological and clinical distinctions, most of the above-mentioned fibrotic disorders have in common a persistent inflammatory stimulus which sustains the production of growth factors, proteolytic enzymes, and pro-fibrogenic cytokines that activate both non-immune (i.e., myofibroblasts, fibroblasts) and immune (i.e., monocytes, macrophages, T-cells) cells, the interactions of which are crucial in the progressive tissue remodeling and destroy. Here we summarize the current status of knowledge regarding the mechanisms implicated in gut fibrosis with a clinical approach, also focusing on possible targets of antifibrogenic therapies.
广泛的组织纤维化是许多影响胃肠道的慢性疾病的终末期过程，包括炎症性肠病（克罗恩病、溃疡性结肠炎）、溃疡性空肠回肠炎和放射性肠炎。纤维化是一种生理修复过程，但如果有害因子持续存在，或者愈合过程过长，它可能会变得有害。在这种情况下，在替换死亡或受损细胞后，纤维化继续用纤维结缔组织替代正常实质组织，导致不受控制的瘢痕形成，最终导致永久性器官损伤、功能丧失和/或狭窄。有几个机制被认为与维持纤维化过程有关。尽管上述大多数纤维化疾病在病因和临床方面存在明显差异，但它们都有一个共同的特点，即持续的炎症刺激，这种刺激持续产生生长因子、蛋白水解酶和促纤维化细胞因子，激活非免疫（即肌成纤维细胞、成纤维细胞）和免疫（即单核细胞、巨噬细胞、T 细胞）细胞，这些细胞的相互作用在进行性组织重塑和破坏中至关重要。在这里，我们从临床角度总结了与肠道纤维化相关的机制的最新知识，还重点介绍了抗纤维化治疗的可能靶点。
