Background and Aims: Transforming growth factors (TGFs) α and β are key regulatory peptides that modulate mucosal cell populations critical to inflammatory bowel disease. The aim of this study was to assess TGF-α and TGF-β expression in human colonic mucosa. Methods: TGF-α and TGF-β expression was assessed in colonic mucosa from patients with ulcerative colitis, patients with Crohn's disease, and controls by Northern blot analysis, in situ hybridization, and bioassay. Results: TGF-α messenger RNA expression localized to the villous tips of the small intestine and the surface epithelium of the colon. TGF-α expression was enhanced 2.3-fold in inactive ulcerative colitis mucosa relative to active ulcerative colitis, Crohn's disease, or normal controls. Enhanced expression correlated with duration of disease. TGF-α expression was increased in affected mucosa from both patients with ulcerative colitis and Crohn's disease with active disease. TGF-β1 messenger RNA expression in ulcerative colitis and Crohn's disease localized mostly to cells of the lamina propria with the highest concentration in inflammatory cells closest to the luminal surface. Conclusions: TGF-α may contribute to epithelial hyperproliferation and the increased risk of malignancy in long-standing ulcerative colitis. TGF-β may be a key cytokine during periods of active inflammation, modulating epithelial cell restitution and functional features of cells within the lamina propria.
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