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Nuclear Receptor FXR: A Potential Therapeutic Target for the Treatment of Diseases with Impaired Urine Concentration

Abstract

Xiaoyan Zhang and Youfei Guan

Farnesoid X receptor (FXR), the bile acid-activated nuclear receptor and member of the nuclear receptor superfamily, plays a key role in bile acid, lipid and glucose homeostasis. FXR is abundantly expressed in the kidney, but its physiological function remains mostly unknown. Recent studies have demonstrated that FXR is expressed in renal collecting ducts where it directly regulates the transcription of the aquaporin 2 (AQP2) gene. FXR gene deficiency results in a polyuric phenotype in mice. These results highlight a novel mechanism for FXR in mediating renal urine concentration independent of the antidiuretic hormone (ADH) system. FXR may represent a potential therapeutic target for treating diseases with urine concentrating defect, including hepatorenal syndrome and nephrogenic diabetes insipitus.

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