One of the most difficult and treatment-resistant complications of Crohn's disease is the development of fibrotic intestinal strictures due to mesenchymal cell hyperplasia and collagen deposition. Resveratrol, a phytoalexin found in berries, peanuts, grapes, and red wine, has been shown to inhibit fibrosis in vasculature, heart, lung, kidney, liver, and esophagus in animal models. Resveratrol has also been shown to inhibit oxidation, inflammation, and cell proliferation and to decrease collagen synthesis in several cell types or animal models. The aim of this study was to determine whether resveratrol has antifibrogenic effects on intestinal smooth muscle cells. Responses to resveratrol by cultured smooth muscle cells isolated from colons of untreated Lewis rats were examined; this rat strain is used in a model of Crohn's disease with prominent intestinal fibrosis. A relative decrease in cell numbers following treatment with 50 and 100μM resveratrol was evident at 24h (p≤0.005). This effect was largely due to cell cycle arrest, with an increase in the percent of cells in S-phase from 8% to 25-35% (p<0.05). Cell viability was unchanged until 2-3d of treatment when there was a 1.2-5.0-fold increase in the percent of apoptotic cells, depending on the assay (p<0.05). Expression of collagen type I protein was decreased following treatment with resveratrol for 24h (to 44% and 25% of control levels with 50 and 100μM resveratrol, respectively; p<0.05). Expression of procollagen types I and III mRNA was also decreased with resveratrol treatment. Resveratrol (50μM) diminished the proliferative response to TGF-β1, as well as IGF-I-stimulated collagen production (p=0.02). Thus, resveratrol decreases intestinal smooth muscle cell numbers through its effects on cell cycle arrest and apoptosis, and also decreases collagen synthesis by the cells. These effects could be useful in preventing the smooth muscle cell hyperplasia and collagen deposition that characterize stricture formation in Crohn's disease.
- Crohn's disease
- inflammatory bowel disease
- Copyright © 2011, American Journal of Physiology- Gastrointestinal and Liver Physiology