Journal
JOURNAL OF DIGESTIVE DISEASES
Volume 17, Issue 8, Pages 501-509Publisher
WILEY
DOI: 10.1111/1751-2980.12378
Keywords
bile acid; cholestasis; enterohepatic circulation; farnesoid X receptor; hepatobiliary transport
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Funding
- Seed Money of Renji Hospital [RJZZ15-012]
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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.
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