BACKGROUND: Bile salts increase intestinal mucosal proliferation through an 
increase in c-Myc, a transcription factor that controls the expression of 
numerous translation regulatory proteins. HuR is an RNA-binding protein that 
regulates translation of target mRNAs. RNA-binding proteins can control mRNA 
stability by binding to AU- and U-rich elements located in the 3'-untranslated 
regions (3'-UTRs) of target mRNAs.
AIM: To determine how bile salt-induced c-Myc stimulates enterocyte 
proliferation.
METHODS: Enterocyte proliferation was measured both in vivo using C57Bl6 mice 
and in vitro using IEC-6 cells after taurodeoxycholate (TDCA) supplementation. 
HuR and c-Myc protein expression was determined by immunoblot. c-Myc mRNA 
expression was determined by PCR. HuR expression was inhibited using specific 
small interfering RNA. HuR binding to c-Myc mRNA was determined by 
immunoprecipitation.
RESULTS: TDCA increased enterocyte proliferation in vivo and in vitro. TDCA 
stimulates translocation of HuR from the nucleus to the cytoplasm. Cytoplasmic 
HuR regulates c-Myc translation by HuR binding to the 3'-UTR of c-Myc mRNA. 
Increased TDCA-induced c-Myc increases enterocyte proliferation.
CONCLUSIONS: Bile salts have beneficial effects on the intestinal epithelial 
mucosa, which are important in maintaining intestinal mucosal integrity and 
function. These data further support an important beneficial role of bile salts 
in regulation of mucosal growth and repair. Decreased enterocyte exposure to 
luminal bile salts, as occurs during critical illness, liver failure, 
starvation, and intestinal injury, may have a detrimental effect on mucosal 
integrity.