Pathogenesis of Intestinal Strictures in Crohnʼs Disease—An Update

Abstract

: Stricture formation in Crohn's disease is a complication of an important wound healing process in the intestine. The smooth muscle cells of the intestinal musculares bear a responsibility for the repair of injured intestine, and effect this wound healing process by proliferating and laying down collagen at the site of injury. Injury in the submucosa, and chronicity of injury, are important factors in the development of stricture. The resultant accumulation of collagenous scar, thickening of the muscle layers, and contracture, all play a role in producing the critical architectural changes in the intestinal wall that impede the aboral movement of chyme. Important putative facets of intestinal smooth muscle cell biology that are involved in stricture formation include: the synthesis and secretion of procollagen; the peculiar response of these cells to cytokines, ascorbate, and corticosteroids; and changes in cell phenotype that result from chronic inflammation. Therapeutic modalities designed to ameliorate the stricturing process will need to modulate these biological activities in resident intestinal smooth muscle cells.

Expression and Regulation of Tissue Inhibitor of Metalloproteinase-1 and Matrix Metalloproteinases by Intestinal Myofibroblasts in Inflammatory Bowel Disease

“…In contrast to ulcerative colitis, intestinal stricture formation because of excessive deposition of fibrous tissue often occurs in patients with Crohn's disease. 2 Although they share a number of clinical, pathological, and immunological similarities, the reason for the frequent development of intestinal strictures in Crohn's disease, but not ulcerative colitis, remains unknown. The turnover of extracellular matrix during the processes of mucosal repair and remodeling is regulated by factors that influence its synthesis and degradation.…”