Bile salts regulate intestinal epithelial cell migration by nuclear factor–κB–induced expression of transforming growth factor–β - 28/08/11

Doi : 10.1016/S1072-7515(03)00720-8

Eric D Strauch, MD ^*^⁎, Jon Yamaguchi, MD ^*, Barbara L Bass, MD, FACS ^*, Jian-Ying Wang, MD, PhD ^*
^* Department of Surgery, University of Maryland, Baltimore, MD, USA

^*Correspondence address: Eric D Strauch, MD, Pediatric Surgery N4E37, 22 S Greene St, Baltimore, MD 21201, USA.

Abstract

Background

Mucosal restitution is an important repair modality in the gastrointestinal tract. We have shown that taurodeoxycholate increases intestinal epithelial cell migration by increasing TGF-β expression, and that the transcription factor NF-κB regulates TDCA induced cell migration after injury. The objectives of this study were to determine if this is a property shared by other bile salts or an effect specific to TDCA, and to determine if NF-κB regulates TGF-β expression.

Study design

Studies were conducted in IEC-6 cells. Cell migration was examined using an in vitro model. TGF-β protein and mRNA expression was determined by ELISA and Northern blot analysis. Sequence-specific NF-κB binding activity was measured by gel shift assays.

Results

Taurocholate and deoxycholate at physiologic concentrations significantly increased intestinal epithelial cell migration 6 hours after wounding (p < 0.01), and was associated with a significant increase in specific NF-κB binding activity. Inhibition of NF-κB activity significantly inhibited cell migration during restitution and resulted in a significant decrease in TGF-β mRNA expression and protein expression.

Conclusions

We conclude that bile salts at physiologic conditions increase cell migration after injury, an effect regulated by NF-κB. Further, NF-κB elicits TGF-β gene transcription during cell migration. These data support a physiologic role of bile salts in the maintenance of intestinal mucosal integrity.

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Abbreviations : DCA, NF-κB, TCA, TDCA, TGF-β