Constitutive Androstane Receptor Differentially Regulates Bile Acid Homeostasis in Mouse Models of Intrahepatic Cholestasis.

ABSTRACT: Bile acid (BA) homeostasis is tightly regulated by multiple transcription factors, including farnesoid X receptor (FXR) and small heterodimer partner (SHP). We previously reported that loss of the FXR/SHP axis causes severe intrahepatic cholestasis, similar to human progressive familial intrahepatic cholestasis type 5 (PFIC5). In this study, we found that constitutive androstane receptor (CAR) is endogenously activated in Fxr:Shp double knockout (DKO) mice. To test the hypothesis that CAR activation protects DKO mice from further liver damage, we generated Fxr;Shp;Car triple knockout (TKO) mice. In TKO mice, residual adenosine triphosphate (ATP) binding cassette, subfamily B member 11 (ABCB11; alias bile salt export pump [BSEP]) function and fecal BA excretion a

SUBMITTER: Kim KH 

PROVIDER: S-EPMC6312660 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature