Table 2.

Molecular targets of FXR in liver and potential beneficial effects of FXR activation in cholestasis.

Molecular targets of FXR in liver	Effects in cholestasis
-Canalicular export of BSs through BSEP and MRP2 -Basolateral BS elimination via OSTα/OSTβ -Inhibition of NTCP- and OATP1B1-mediated BS uptake -Inhibition of BS synthesis (inhibition of CYP7A1 through FGF19- and SHP- mediated mechanisms, inhibition of CYP8B1and CYP27A1) -Promotion of BS detoxification (through upregulation of CYP3A4, SULT2A1, UGT2B4)	Reduction of intracellular BS toxicity
-Reduced biliary excretion of BSs through inhibition of synthesis -Canalicular PL secretion through MDR3 and promotion of mixed micelle formation -Promotion of ${\text{HCO}}_3^{-}$ -rich bile secretion through carbonic anhydrase 14 -Induction of gallbladder secretion via VPAC-1	Reduction of bile toxicity
-Repression of pro-inflammatory gene expression through interaction with NF-κB	Inhibition of inflammation