FXR: a target for cholestatic syndromes?

Abstract

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 OSTα-OSTβ 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.

Keywords::

• bile acid
• cholestatic liver disease
• farnesoid X receptor (FXR)

Acknowledgements

This work was supported by USPHS grants DK 25636, the Yale Liver Center DK P30-34989 and ES 03828.