title: Role of farnesoid X receptor in cholestasis.
abstract: The nuclear receptor farnesoid X receptor (FXR) plays an important role in physiological bile acid synthesis, secretion and transport. Defects of FXR regulation in these processes can cause cholestasis and subsequent pathological changes. FXR regulates the synthesis and uptake of bile acid via enzymes. It also increases bile acid solubility and elimination by promoting conjugation reactions and exports pump expression in cholestasis. The changes in bile acid transporters are involved in cholestasis, which can result from the mutations of transporter genes or acquired dysfunction of transport systems, such as inflammation-induced intrahepatic cholestasis. The modulation function of FXR in extrahepatic cholestasis is not identical to that in intrahepatic cholestasis, but the discrepancy may be reduced over time. In extrahepatic cholestasis, increasing biliary pressure can induce bile duct proliferation and bile infarcts, but the absence of FXR may ameliorate them. This review provides an update on the function of FXR in the regulation of bile acid metabolism, its role in the pathophysiological process of cholestasis and the therapeutic use of FXR agonists.
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Zhi Qing
authors.initials: ZQ
authors.lastname: Yuan
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. keweipig@126.com.
authors.forename: Ke Wei
authors.initials: KW
authors.lastname: Li
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism; D002779:Cholestasis / Q000188:drug therapy / Q000378:metabolism*; D001651:Cholestasis, Extrahepatic / Q000188:drug therapy / Q000378:metabolism; D002780:Cholestasis, Intrahepatic / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000502:physiology*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated
keywords: bile acid; cholestasis; enterohepatic circulation; farnesoid X receptor; hepatobiliary transport