Burke John P, Mulsow Jurgen J, O'Keane Conor, Docherty Neil G, Watson R William G, O'Connell P Ronan
Department of Surgery, Mater Misericordiae University Hospital and UCD School of Medicine and Medical Sciences, Dublin, Ireland.
Am J Gastroenterol. 2007 Feb;102(2):439-48. doi: 10.1111/j.1572-0241.2006.01010.x. Epub 2006 Dec 11.
Over one-third of patients with Crohn's disease (CD) will develop an intestinal stricture and the great majority of these will require at least one surgical procedure. While the pathogenesis of inflammation in CD has been extensively investigated, knowledge of stricture pathogenesis remains limited. The aim of this review is to discuss the current understanding of fibrogenesis in CD and to outline potential directions in research and therapeutics.
The electronic literature (January 1966 to May 2006) on CD-associated fibrosis was reviewed. Further references were obtained by cross-referencing from key articles.
CD-associated fibrosis results from chronic transmural inflammation and a complex interplay among intestinal mesenchymal cells, cytokines, and local inflammatory cells. The fibroblast is the key cell type mediating stricture formation. The cytoarchitecure of the bowel wall is altered with disruption of the muscularis mucosa, thickening of the muscularis propria, and deposition of collagen throughout. The cytokine TGF-beta appears critical in this process, acting to increase growth factor and extracellular matrix (ECM) production and dysregulate ECM turnover. Potential therapeutic interventions are likely to concentrate on modulating down-stream targets of TGF-beta.
Greater understanding of the biology of fibrostenosis is likely to yield significant advances in our ability to care for patients with stricturing CD. Potential dividends of this approach include identification of novel therapeutic targets and biomarkers useful for prognostication and therapeutic monitoring.
超过三分之一的克罗恩病（CD）患者会出现肠道狭窄，其中绝大多数患者至少需要接受一次外科手术。虽然CD炎症的发病机制已得到广泛研究，但对狭窄发病机制的了解仍然有限。本综述的目的是讨论目前对CD中纤维生成的理解，并概述研究和治疗的潜在方向。
回顾了1966年1月至2006年5月关于CD相关纤维化的电子文献。通过对关键文章的交叉引用获得了更多参考文献。
CD相关纤维化是由慢性透壁性炎症以及肠道间充质细胞、细胞因子和局部炎症细胞之间的复杂相互作用引起的。成纤维细胞是介导狭窄形成的关键细胞类型。肠壁的细胞结构发生改变，黏膜肌层破坏、固有肌层增厚以及胶原纤维弥漫性沉积。细胞因子转化生长因子-β（TGF-β）在这一过程中似乎起关键作用，它可增加生长因子和细胞外基质（ECM）的产生，并使ECM周转失调。潜在的治疗干预可能集中在调节TGF-β的下游靶点。
对纤维性狭窄生物学的更深入了解可能会在我们治疗狭窄性CD患者的能力方面取得重大进展。这种方法的潜在益处包括识别新的治疗靶点和可用于预后评估及治疗监测的生物标志物。
