Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty at Heinrich-Heine-University, Düsseldorf, Germany.
Semin Liver Dis. 2018 Nov;38(4):333-339. doi: 10.1055/s-0038-1669940. Epub 2018 Oct 24.
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.
TGR5（GPBAR1）是一种被初级和次级胆汁酸激活的 G 蛋白偶联受体，它在肝脏的不同非实质细胞中表达，如窦状内皮细胞、枯否细胞、胆管细胞以及活化的肝星状细胞。在肝脏中，TGR5 调节微循环、炎症、再生、胆汁分泌和增殖以及胆囊充盈。TGR5 缺失使小鼠更容易受到感染、炎症、代谢和胆汁淤积性肝损伤的影响。目前尚不清楚 TGR5 是否在人类非酒精性脂肪性肝炎和胆汁淤积性肝病（如原发性硬化性胆管炎和原发性胆汁性胆管炎）的发病机制中发挥作用。然而，TGR5 在人类肝内外胆管癌以及囊性胆管细胞中过度表达，在这些细胞中，受体促进细胞增殖、抗凋亡和囊泡生长。虽然 TGR5 激动剂可能改善代谢、炎症和胆汁淤积性肝病的各个方面，但 TGR5 抑制剂可能减轻多囊肝病和胆管癌的疾病进展。
