Pharmacology of bile acid receptors: Evolution of bile acids from simple detergents to complex signaling molecules. Bile acid receptors in the biliary tree: TGR5 in physiology and disease. Α5 β1-integrins are sensors for tauroursodeoxycholic acid in hepatocytes. Hepatology 2007 45 (03) 695-704Įxpression and function of the bile acid receptor TGR5 in Kupffer cells. The G-protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells. A G protein–coupled receptor responsive to bile acids. Identification of membrane-type receptor for bile acids (M-BAR). Science 1999 284 (5418): 1365-1368Įndogenous bile acids are ligands for the nuclear receptor FXR/BAR. Bile acids: natural ligands for an orphan nuclear receptor. Identification of a nuclear receptor for bile acids. 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. 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. 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. Absence of TGR5 renders mice more susceptible toward infectious, inflammatory, metabolic as well as cholestatic liver injuries. In liver, TGR5 modulates microcirculation, inflammation, regeneration, biliary secretion and proliferation as well as gallbladder filling. 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. Buy Article Permissions and Reprints Abstract
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