title: Bile salts increase epithelial cell proliferation through HuR-induced c-Myc expression.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Pediatric Surgery, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Perrone
authors.forename: Lan
authors.initials: L
authors.lastname: Liu
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Turner
authors.forename: Eric D
authors.initials: ED
authors.lastname: Strauch
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism*; D020895:Enterocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013657:Taurodeoxycholic Acid / Q000378:metabolism / Q000494:pharmacology
chemical_list: D020413:3' Untranslated Regions; D001647:Bile Acids and Salts; D051959:ELAV Proteins; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013657:Taurodeoxycholic Acid