FXR: a target for cholestatic syndromes?
The nuclear farnesoid X receptor (FXR) plays a pivotal role in maintaining bile acid homeostasis by regulating key genes involved in bile acid synthesis, metabolism and transport, including CYP7A1, UGT2B4, BSEP, MDR3, MRP2, ASBT, I-BABP, NTCP and OSTalpha-OSTbeta in humans. Altered expression or malfunction of these genes has been described in patients with cholestatic liver diseases. This review examines the rationale for the use of FXR ligand therapy in various cholestatic liver disorders and includes potential concerns.
Cai
Shi-Ying
SY
Liver Center, Department of Medicine, Yale University School of Medicine, P.O. Box 208019, New Haven, CT 06520-8019, USA.
Boyer
James L
JL
D000818:Animals; D002779:Cholestasis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D018160:Receptors, Cytoplasmic and Nuclear; D013577:Syndrome; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000099150:Receptor, Farnesoid X-Activated
D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated