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-beta expression, and that the transcription factor NF-kappa B 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-kappa B regulates TGF-beta expression. STUDY DESIGN: Studies were conducted in IEC-6 cells. Cell migration was examined using an in vitro model. TGF-beta protein and mRNA expression was determined by ELISA and Northern blot analysis. Sequence-specific NF-kappa B 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-kappa B binding activity. Inhibition of NF-kappa B activity significantly inhibited cell migration during restitution and resulted in a significant decrease in TGF-beta mRNA expression and protein expression. CONCLUSIONS: We conclude that bile salts at physiologic conditions increase cell migration after injury, an effect regulated by NF-kappa B. Further, NF-kappa B elicits TGF-beta gene transcription during cell migration. These data support a physiologic role of bile salts in the maintenance of intestinal mucosal integrity.
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-beta expression, and that the transcription factor NF-kappa B 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-kappa B regulates TGF-beta expression. STUDY DESIGN: Studies were conducted in IEC-6 cells. Cell migration was examined using an in vitro model. TGF-beta protein and mRNA expression was determined by ELISA and Northern blot analysis. Sequence-specific NF-kappa B 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-kappa B binding activity. Inhibition of NF-kappa B activity significantly inhibited cell migration during restitution and resulted in a significant decrease in TGF-beta mRNA expression and protein expression. CONCLUSIONS: We conclude that bile salts at physiologic conditions increase cell migration after injury, an effect regulated by NF-kappa B. Further, NF-kappa B elicits TGF-beta gene transcription during cell migration. These data support a physiologic role of bile salts in the maintenance of intestinal mucosal integrity.
Authors: Douglas J Turner; Samuel M Alaish; Tongtong Zou; Jaladanki N Rao; Jian-Ying Wang; Eric D Strauch Journal: Ann Surg Date: 2007-03 Impact factor: 12.969
Authors: Sidhartha R Sinha; Yeneneh Haileselassie; Linh P Nguyen; Carolina Tropini; Min Wang; Laren S Becker; Davis Sim; Karolin Jarr; Estelle T Spear; Gulshan Singh; Hong Namkoong; Kyle Bittinger; Michael A Fischbach; Justin L Sonnenburg; Aida Habtezion Journal: Cell Host Microbe Date: 2020-02-25 Impact factor: 21.023