| TGR5 in the Biliary Tree. | |
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MedLine Citation:
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PMID: 21691103 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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Verena Keitel; Dieter Häussinger |
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Publication Detail:
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Type: Journal Article Date: 2011-06-17 |
Journal Detail:
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Title: Digestive diseases (Basel, Switzerland) Volume: 29 ISSN: 1421-9875 ISO Abbreviation: Dig Dis Publication Date: 2011 |
Date Detail:
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Created Date: 2011-06-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8701186 Medline TA: Dig Dis Country: Switzerland |
Other Details:
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Languages: eng Pagination: 45-7 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 S. Karger AG, Basel. |
Affiliation:
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Clinic of Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Düsseldorf, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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