Bile salts increase epithelial cell proliferation through HuR-induced c-Myc expression.

Area of Science:

• Gastroenterology
• Molecular Biology
• Cell Biology

Background:

• Bile salts stimulate intestinal mucosal proliferation via c-Myc, a key transcription factor.
• HuR (human antigen R) is an RNA-binding protein regulating mRNA translation and stability.
• RNA-binding proteins interact with 3'-untranslated regions (3'-UTRs) of target mRNAs.

Purpose of the Study:

• To elucidate the mechanism by which bile salt-induced c-Myc stimulates enterocyte proliferation.

Main Methods:

• Enterocyte proliferation assessed in vivo (mice) and in vitro (IEC-6 cells) with taurodeoxycholate (TDCA).
• HuR and c-Myc protein levels measured by immunoblot; c-Myc mRNA by PCR.
• HuR knockdown via small interfering RNA and HuR-c-Myc mRNA interaction by immunoprecipitation.

Main Results:

• TDCA significantly increased enterocyte proliferation in both models.
• TDCA induced HuR translocation from the nucleus to the cytoplasm.
• Cytoplasmic HuR binds to the 3'-UTR of c-Myc mRNA, enhancing its translation and subsequently enterocyte proliferation.

Conclusions:

• Bile salts exert beneficial effects on intestinal epithelial mucosa, crucial for mucosal integrity and function.
• These findings highlight a significant role for bile salts in regulating mucosal growth and repair.
• Reduced enterocyte exposure to bile salts, seen in critical illness or injury, may compromise mucosal integrity.