Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling

Area of Science:

• Gastroenterology
• Cell Biology
• Microbiology

Background:

• Bile acids (BAs) are synthesized in the liver and metabolized by gut bacteria into potentially harmful secondary forms.
• Secondary BAs can injure the intestine and are implicated in various diseases.
• Epidermal growth factor receptor (EGFR) and farnesoid X receptor (FXR) are known to interact with BAs.

Purpose of the Study:

• To investigate the effects of BAs on intestinal epithelial cell proliferation.
• To explore the roles of EGFR and FXR in mediating these BA-induced effects.

Main Methods:

• Treatment of intestinal cells with taurine-conjugated cholic acid (TCA) and deoxycholic acid (DCA).
• Assessment of cell proliferation and protein phosphorylation (Src, EGFR, ERK 1/2).
• Pharmacological inhibition and genetic ablation (EGFR) or siRNA (FXR) to block signaling pathways.

Main Results:

• TCA induced proliferation, stimulating Src, EGFR, and ERK 1/2 phosphorylation; blockade of these pathways abrogated TCA's effect.
• EGFR and Src activation were interdependent.
• DCA inhibited proliferation and diminished EGFR phosphorylation; FXR blockade abolished DCA's inhibitory effect.
• DCA's mechanism may involve FXR-dependent inactivation of the EGFR/Src/ERK pathway.

Conclusions:

• TCA promotes intestinal cell proliferation through Src, EGFR, and ERK activation.
• DCA inhibits proliferation via an FXR-dependent pathway, potentially involving EGFR/Src/ERK inactivation.
• Altered gut microbiota and secondary BA production may influence intestinal epithelial cell proliferation in health and disease.