Transforming growth factor-beta1 and its receptors in patients with ulcerative colitis.

Transforming growth factor-beta1 (TGF-beta1) plays a role in the pathogenesis of ulcerative colitis (UC) by activating its specific receptors (T beta RI-T beta RIII). We investigated the expression of genes encoding for TGF-beta1 and T beta RI-III using RT-QPCR in patients with active and inactive UC and non-IBD controls. The localization and level of TGF-beta1 protein in intestinal tissue was estimated by immunohistochemistry, and serum TGF-beta1 concentrations were determined using ELISA. We found a significant increase in TGF-beta1 gene expression and increase in the expression of genes encoding receptor T beta RI in patients with active UC when compared with controls. The expression of genes encoding T beta RII was found to be higher in patients with both active and inactive UC when compared to controls. Specific staining for TGF-beta1 in fibroblasts was significantly greater in both active and inactive UC as compared to controls. The serum concentration of TGF-beta1 was significantly higher in patients with active UC when compared with controls as well as in UC patients with left side/total colonic extension when compared with those with disease limited to rectum/rectosigmoid area. However, no correlation between TGF-beta1 serum concentrations and UC activity index was found. Increases in TGF-beta1 gene expression and its protein level, associated with altered TGF-beta1 receptor profile indicate a functional role for TGF-beta1 in intestinal inflammatory/repair processes in UC. Increases in TGF-beta1 serum concentrations correlate with extension of disease.