Background: In addition to aiding in the digestion of fats, luminal bile salts have been shown to modulate gastrointestinal epithelial growth, differentiation, and other functions. We hypothesized that bile acids could modulate the intestinal mucosal repair process of restitution. We investigated the effect of the bile salt taurodeoxycholic acid on epithelial migration and identified a role for TGFbeta, a widely expressed cytokine in the intestinal villus, in this repair process.
Methods: Using a well-established model of epithelial restitution, IEC-6 cells were plated on 60-mm Matrigel-coated plastic dishes and grown to confluence. The epithelium was wounded by scraping with a 6-mm-wide blade to create a smooth denuded edge and cell migration was measured 8 h later. Cells were grown in control DMEM with 5% FBS with or without 0.01-2 mM taurodeoxycholic acid (TDCA). In parallel experiments, cells were harvested for Northern analysis of TGFbeta and GAPDH expression; [3H]thymidine uptake was used to measure proliferation. Anti-TGFbeta antibody was added to cells grown in the presence of 0.05 mM TDCA and migration was measured at 8 h.
Results: TDCA at physiologic luminal concentrations augments IEC-6 cell migration, with a maximal effect at 0.05 mM. TDCA inhibited proliferation at these concentrations. TGFbeta expression increased in response to bile acid, while wounding had less of an effect on TGFbeta expression. Blockade of TGFbeta function with TGFbeta antibody eliminated the effect of bile on cell migration.
Conclusions: Bile acid at physiologic concentrations augments small intestinal epithelial cell migration. The process is dependent on TGFbeta and is independent of cell division. The data further support a role for bile acids and TGFbeta in differentiated intestinal cell function and in preservation of an intact mucosa.
Copyright 2001 Academic Press.