Fig. 10.

Interrelationship between FXRα1 and FXRα2. The effects of FXRα1 on FXRα2-mediated transactivation of (A) human IR1a element reporter pGL3/p-2xhIR1a and (B) full-length human BSEP promoter reporter phBSEP(-2.6kb) were investigated. Increasing amounts of FXRα1 were cotransfected with a constant amount of FXRα2 and pGL3/p-2xhIR1a or phBSEP(-2.6kb). Vector pcDNA5 plasmid DNAs were also cotransfected to obtain a constant total plasmid DNA in each well. Sixteen hours posttransfection, cells were treated with DMSO (0.1%) or CDCA (10 μM) for 30 h, followed by detection of luciferase activity. The data are presented as mean ± SD of at least three repeated experiments. (C) A diagram summarizing FXRα1- and FXRα2-mediated transactivation of BSEP through IR1a and IR1b. In human, FXRα1 and FXRα2 regulate BSEP exclusively through IR1b and hIR1a, respectively. In mouse and rat, FXRα1 is able to transactivate BSEP through both m/rIR1a and IR1b, whereas FXRα2 transactivates exclusively through m/rIR1a.