Document Detail


TGR5 in the Biliary Tree.
MedLine Citation:
PMID:  21691103     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Background/Aims: TGR5 is a plasma membrane-bound, G-protein-coupled receptor for bile acids. TGR5 mRNA has been detected in a variety of tissues, including liver. The aim of the present study was to determine the localization and function of the receptor in biliary epithelial cells. Methods: Liver and gallbladder tissue from humans and rodents were analyzed for TGR5 expression and localization by real-time PCR, Western blot and immunofluorescence microscopy. Cholangiocytes and gallbladder epithelial cells were isolated from wild-type and TGR5 knockout mice. Cyclic AMP (cAMP) was measured using a radioimmunoassay and chloride concentrations were analyzed using the chloride-sensitive dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE). Cell proliferation was determined by bromodeoxyuridine incorporation. Results: TGR5 is localized in the apical membrane and the primary cilium of cholangiocytes and gallbladder epithelial cells. Activation of the receptor by bile acids led to a rise in intracellular cAMP concentrations and a decrease in intracellular chloride concentrations as measured by MQAE fluorescence, indicating increased chloride secretion. This effect could be abolished in the presence of an inhibitor of the cAMP-dependent chloride channel cystic fibrosis transmembrane conductance regulator. Furthermore, activation of TGR5 by bile acids induced cholangiocyte proliferation, which was not observed in cells derived from TGR5 knockout mice. Conclusion: In biliary epithelial cells, TGR5 acts as a bile acid sensor coupling biliary bile acid concentrations to bile formation. Furthermore, the receptor may play a role in bile acid-dependent cholangiocyte proliferation and may protect biliary epithelial cells from bile acid-induced cell death.
Authors:
Verena Keitel; Dieter Häussinger
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Publication Detail:
Type:  Journal Article     Date:  2011-06-17
Journal Detail:
Title:  Digestive diseases (Basel, Switzerland)     Volume:  29     ISSN:  1421-9875     ISO Abbreviation:  Dig Dis     Publication Date:  2011  
Date Detail:
Created Date:  2011-06-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8701186     Medline TA:  Dig Dis     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  45-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 S. Karger AG, Basel.
Affiliation:
Clinic of Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Düsseldorf, Germany.
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