Taurodeoxycholate increases intestinal epithelial cell proliferation through c-myc expression.

Abstract

BACKGROUND: Bile salts have been shown to modulate gastrointestinal epithelial restitution, differentiation, and other functions. Prior studies have shown that the bile salt taurodeoxycholate increases cell migration after injury. The purpose of this experiment was to determine the effect that taurodeoxycholate has on intestinal epithelial cell growth, c-myc expression and function. METHODS: IEC-6 or Caco-2 cells were treated with varying concentrations of taurodeoxycholate (.05 to 1 mmol/L) and proliferation determined. Apoptosis was measured by use of DNA fragmentation assay and nuclear staining. Cell phase was determined with propidium iodide flow cytometry. C-myc expression was determined by Northern and Western blot analysis, and c-myc function was inhibited by specific c-myc antisense. RESULTS: There was no change in cell structure. Apoptosis was not induced. Six days after exposure to taurodeoxycholate, IEC-6 cell proliferation was significantly increased. Flow cytometry showed a significant increase in S-phase concentration and a significant decrease in G1-phase concentration of the cell cycle. Taurodeoxycholate also increased c-myc protein and mRNA expression, and inhibition of c-myc function prevented taurodeoxycholate-induced cell proliferation. CONCLUSIONS: Exposure to physiological concentrations of the bile salt taurodeoxycholate increases intestinal epithelial cell proliferation. This effect is at least partially mediated through a c-myc-dependent mechanism. Bile salts can have a beneficial effect on the intestinal mucosa.