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Semin Liver Dis 2018; 38(04): 333-339
DOI: 10.1055/s-0038-1669940
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Role of TGR5 (GPBAR1) in Liver Disease

Verena Keitel
1   Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty at Heinrich-Heine-University, Düsseldorf, Germany
,
Dieter Häussinger
1   Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty at Heinrich-Heine-University, Düsseldorf, Germany
› Author Affiliations Funding This study was supported by Deutsche Forschungsgemeinschaft (DFG) through SFB 974 and KFO 217.
Further Information

Publication History

Publication Date:
24 October 2018 (online)

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Abstract

TGR5 (GPBAR1) is a G protein–coupled receptor activated by primary and secondary bile acids, which is expressed in different nonparenchymal cells of the liver, such as sinusoidal endothelial cells, Kupffer cells, cholangiocytes as well as activated hepatic stellate cells. In liver, TGR5 modulates microcirculation, inflammation, regeneration, biliary secretion and proliferation as well as gallbladder filling. Absence of TGR5 renders mice more susceptible toward infectious, inflammatory, metabolic as well as cholestatic liver injuries. It is unknown whether TGR5 plays a role in the pathogenesis of human nonalcoholic steatohepatitis and cholestatic liver diseases such as primary sclerosing cholangitis and primary biliary cholangitis. However, overexpression of TGR5 has been detected in human intra- and extrahepatic cholangiocarcinoma as well as in cystic cholangiocytes, where the receptor promotes cell proliferation, anti-apoptosis as well as cyst growth. While TGR5 agonists may improve various aspects of metabolic, inflammatory, and cholestatic liver diseases, TGR5 inhibitors may attenuate disease progression in polycystic liver disease and cholangiocarcinoma.

Keywords

bile acids - G protein–coupled receptor - steatohepatitis - cholangiopathy - inflammation
 

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