Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center; Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China.
Mucosal Immunol. 2018 Mar;11(2):294-303. doi: 10.1038/mi.2017.107. Epub 2017 Dec 20.
Crohn's disease (CD) is often accompanied by the complications of intestinal strictures and fistulas. These complications remain obstacles in CD treatment. In recent years, the importance of epithelial-mesenchymal transition in the pathogenesis of CD-associated fistulas and intestinal fibrosis has become apparent. Epithelial-mesenchymal transition refers to a dynamic change, wherein epithelial cells lose their polarity and adherence and acquire migratory function and fibroblast features. During formation of CD-associated fistulas, intestinal epithelial cells dislocate from the basement membrane and migrate to the lining of the fistula tracts, where they convert into transitional cells as a compensatory response under the insufficient wound healing condition. In CD-associated intestinal fibrosis, epithelial-mesenchymal transition may serve as a source of new fibroblasts and consequently lead to overproduction of extracellular matrix. In this review, we present current knowledge of epithelial-mesenchymal transition and its role in the pathogenesis of CD in order to highlight new therapy targets for the associated complications.
克罗恩病(CD)常伴有肠狭窄和瘘管等并发症。这些并发症仍然是 CD 治疗的障碍。近年来,上皮-间充质转化在 CD 相关瘘管和肠纤维化发病机制中的重要性已变得明显。上皮-间充质转化是指一种动态变化,其中上皮细胞失去极性和黏附性,并获得迁移功能和成纤维细胞特征。在 CD 相关瘘管形成过程中,肠上皮细胞从基底膜脱落并迁移到瘘管衬里,在愈合条件不足的情况下,作为一种代偿反应,它们转化为过渡细胞。在 CD 相关肠纤维化中,上皮-间充质转化可能作为新成纤维细胞的来源,并导致细胞外基质的过度产生。在这篇综述中,我们介绍了上皮-间充质转化及其在 CD 发病机制中的作用的最新知识,以强调相关并发症的新治疗靶点。