Document Detail

Modulation of steady-state messenger RNA levels in the regenerating rat liver with bile acid feeding.
MedLine Citation:
PMID:  11303292     Owner:  NLM     Status:  MEDLINE    
Liver regeneration after two thirds partial hepatectomy (PH) is an orchestrated hyperplastic growth process requiring coordinated expression of many genes. The synchronous progression of 95% of the remnant hepatocytes through the cell cycle provides an in vivo model for examining the influence of bile acids on the molecular regulation of hepatocyte replication and growth. In this study, we examined the effects of endogenous deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) on messenger RNA (mRNA) expression and growth rate during liver regeneration. Rats were fed diets containing no addition, 0.4% DCA, UDCA, or both for 14 days; they then underwent 70% PH and were maintained on the diets for an additional 14 days. mRNA transcript levels for a variety of cell cycle-regulated genes were examined post-PH by Northern blot analysis. Bile acid concentrations were determined in liver, isolated nuclei, and plasma by gas chromatography and mass spectrometry. The results indicated that the addition of DCA and UDCA to the diet markedly shifted the bile-acid compositions of liver and plasma. In addition, DCA dramatically altered the abundance of many transcripts post-PH, whereas coadministration of UDCA suppressed the effect. DCA feeding significantly inhibited liver growth through day 3; however, by day 8, it induced an approximately 20% increase in mass compared with controls, UDCA-fed, or combination-fed animals. UDCA was concentrated greater than 20-fold in nuclei compared with whole liver in controls and DCA-fed animals and greater than 2-fold with UDCA feeding. These data suggest that bile acids may have a key role in liver regeneration, which is significantly altered by modulation of the bile-acid pool.
B T Kren; C M Rodrigues; K D Setchell; C J Steer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society     Volume:  7     ISSN:  1527-6465     ISO Abbreviation:  Liver Transpl.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-04-16     Completed Date:  2001-06-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100909185     Medline TA:  Liver Transpl     Country:  United States    
Other Details:
Languages:  eng     Pagination:  321-34     Citation Subset:  IM    
Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
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MeSH Terms
Bile Acids and Salts / physiology*
Blotting, Northern
Deoxycholic Acid / pharmacology
Extracellular Matrix / genetics
Gene Expression
Liver Regeneration / genetics*,  physiology
Proto-Oncogene Proteins / physiology
RNA, Messenger / analysis*
Rats, Sprague-Dawley
Ursodeoxycholic Acid / pharmacology
Reg. No./Substance:
0/Bile Acids and Salts; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 128-13-2/Ursodeoxycholic Acid; 83-44-3/Deoxycholic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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