Fig. 3.

(A) FXR mRNA was downregulated in all cell lines and primary human hepatocytes (PHH) tested. (B) FXR protein levels were similarly disrupted in all cell lines. (C) CDCA (50 μM) and GW4064 (300 nM) significantly increased FXR–GAL4 luciferase reporter activity in CHO cells, and such activity was reduced by a known inhibitor (DY268; 370 nM) and mithramycin (300 nM). (D) Mithramycin increased expression of SHP in Huh7 and HepaRG cell lines. (E) Mithramycin did not affect GCDC-induced cellular toxicity in HepaRG cells, whereas mithramycin resulted in additional GCDC toxicity in HepaRG BSEP knockout cells. *P < 0.05; **P < 0.01; and ****P < 0.0001.