PMID- 22626558 OWN - NLM STAT- MEDLINE DCOM- 20130110 LR - 20211021 IS - 1095-8673 (Electronic) IS - 0022-4804 (Print) IS - 0022-4804 (Linking) VI - 178 IP - 1 DP - 2012 Nov TI - Bile salts increase epithelial cell proliferation through HuR-induced c-Myc expression. PG - 155-64 LID - S0022-4804(12)00131-X [pii] LID - 10.1016/j.jss.2012.02.029 [doi] AB - 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. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Perrone, Erin E AU - Perrone EE AD - Department of Pediatric Surgery, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. FAU - Liu, Lan AU - Liu L FAU - Turner, Douglas J AU - Turner DJ FAU - Strauch, Eric D AU - Strauch ED LA - eng GR - R21 DK075409/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20120510 PL - United States TA - J Surg Res JT - The Journal of surgical research JID - 0376340 RN - 0 (3' Untranslated Regions) RN - 0 (Bile Acids and Salts) RN - 0 (ELAV Proteins) RN - 0 (Myc protein, mouse) RN - 0 (Proto-Oncogene Proteins c-myc) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 516-50-7 (Taurodeoxycholic Acid) SB - IM MH - 3' Untranslated Regions/genetics MH - Animals MH - Bile Acids and Salts/metabolism/*pharmacology MH - Cell Line MH - Cell Proliferation/drug effects MH - Cytoplasm/metabolism MH - ELAV Proteins/genetics/*metabolism MH - Enterocytes/cytology/drug effects/metabolism MH - Epithelial Cells/cytology/drug effects/metabolism MH - Gene Expression/drug effects/physiology MH - Intestinal Mucosa/*cytology/drug effects/*metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Proto-Oncogene Proteins c-myc/*genetics/metabolism MH - RNA, Messenger/metabolism MH - RNA, Small Interfering/genetics MH - Taurodeoxycholic Acid/metabolism/pharmacology PMC - PMC3593244 MID - NIHMS372873 EDAT- 2012/05/26 06:00 MHDA- 2013/01/11 06:00 PMCR- 2013/11/01 CRDT- 2012/05/26 06:00 PHST- 2011/04/05 00:00 [received] PHST- 2012/01/05 00:00 [revised] PHST- 2012/02/16 00:00 [accepted] PHST- 2012/05/26 06:00 [entrez] PHST- 2012/05/26 06:00 [pubmed] PHST- 2013/01/11 06:00 [medline] PHST- 2013/11/01 00:00 [pmc-release] AID - S0022-4804(12)00131-X [pii] AID - 10.1016/j.jss.2012.02.029 [doi] PST - ppublish SO - J Surg Res. 2012 Nov;178(1):155-64. doi: 10.1016/j.jss.2012.02.029. Epub 2012 May 10.