Stenke Emily, Bourke Billy, Knaus Ulla
School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
Department of Pediatric Gastroenterology, Our Lady's Children's Hospital, Dublin, Ireland.
Front Pediatr. 2017 Jun 16;5:141. doi: 10.3389/fped.2017.00141. eCollection 2017.
Crohn's disease (CD) is a lifelong inflammatory bowel disease with a rapidly rising incidence in the pediatric population. A common complication of CD is the development of fibrotic strictures, which may be present at initial diagnosis or develop many years later. Clinical presentation depends on stricture location and degree of obstruction, and strictures frequently contain a mixture of inflammatory and fibrotic tissue. Histological examination of Crohn's strictures shows thickening of the muscular layers and the submucosa, where increased collagen deposition by activated myofibroblasts is concentrated around islands of smooth muscle cells and at the superficial margin of the muscularis propria. No antifibrotic therapies for Crohn's strictures exist. Profibrotic transforming growth factor-β (TGFβ)/bone morphogenetic protein signaling stimulates myofibroblast differentiation and extracellular matrix deposition. Understanding and targeting TGFβ1 downstream signaling is the main focus of current research, raising the possibility of specific antifibrotic therapy in CD becoming available in the future.
克罗恩病(CD)是一种终身性炎症性肠病,在儿科人群中的发病率迅速上升。CD的一种常见并发症是纤维化狭窄的形成,其可能在初次诊断时就已存在,或在多年后出现。临床表现取决于狭窄的位置和梗阻程度,且狭窄通常包含炎症组织和纤维化组织的混合物。对克罗恩病狭窄的组织学检查显示肌层和黏膜下层增厚,其中活化的肌成纤维细胞增加的胶原蛋白沉积集中在平滑肌细胞岛周围和固有肌层的浅表边缘。目前尚无针对克罗恩病狭窄的抗纤维化疗法。促纤维化的转化生长因子-β(TGFβ)/骨形态发生蛋白信号传导刺激肌成纤维细胞分化和细胞外基质沉积。理解并靶向TGFβ1下游信号传导是当前研究的主要重点,这增加了未来在CD中获得特异性抗纤维化疗法的可能性。