Transforming growth factor-beta s and their signaling receptors are coexpressed in Crohn's disease

Objective To evaluate mechanisms that contribute to tissue repair and tissu e remodeling in Crohn's disease (CD). Summary Background Data Transforming growth factor-beta s (TGF-beta s) are involved in different chronic inflammatory disorders. They function by bind ing to two receptors, type I (T beta R-I) subtype ALK5 and type II (T beta R-II), which are concomitantly required for signal transduction. Methods Tissues were obtained from 18 patients with CD (10 female patients, 8 male patients, median age 38.7 years [range 16 to 58 years]) undergoing surgery because of CD-related complications. Tissue samples of 18 healthy o rgan donors (10 female subjects, 8 male subjects, median age 50.3 years [ra nge 15 to 65 years]) sewed as controls. The expression and localization of TGF-beta 1, TGF-beta 2, TGF-beta 3, T beta R-I-ALK5, T beta R-II, and T bet a R-III were studied by Northern blot analysis, in situ hybridization, and immunohistochemistry. Results On Northern blot analysis, 94% of the CD samples exhibited enhanced TGF-beta 1, TGF-beta 3, and T beta R-II mRNA expression compared with cont rols. TGF-beta 2 was increased in 72%, T beta R-I-ALK5 in 72%, and T beta R -III in 82% of the patients with CD. On in situ hybridization and immunohis tochemical analysis, TGF-beta 1, T beta R-I-ALK5, and T beta R-II were seen to be colocalized in the lamina propria cells and in the lymphocytes close st to the luminal surface, but also in the remaining epithelial cells, and in fibroblasts of CD tissue samples. Conclusions The concomitant overexpression of TGF-Ps and their signaling re ceptors in CD points to a potential role of these regulatory molecules in t he pathophysiology of CD. Activation of TGF-P-mediated pathways might promo te the repair of mucosal injury by enhancing the process of reepithelizatio n, but might also contribute to extracellular matrix generation and subsequ ently to intramural fibrosis and intestinal obstruction.