Non-steroidal FXR agonist cilofexor improves cholestatic liver injury in the Mdr2^-/- mouse model of sclerosing cholangitis.

ABSTRACT:

Background & aims

The nuclear receptor farnesoid X receptor (FXR) is a key regulator of hepatic bile acid (BA) and lipid metabolism, inflammation and fibrosis. Here, we aimed to explore the potential of cilofexor (GS-9674), a non-steroidal FXR agonist, as a therapeutic approach for counteracting features of cholestatic liver injury by evaluating its efficacy and mechanisms in the Mdr2/Abcb4 knockout (^-/-) mouse model of sclerosing cholangitis.

Methods

FVB/N wild-type and Mdr2^-/- or BALB/c wild-type and Mdr2^-/- mice were treated with 0, 10, 30 or 90 mg/kg cilofexor by gavage every 24 h for 10 weeks. Serum biochemistry, gene expression profile, hydroxyproline content, and picrosirius red and F4/80 immunostaini

SUBMITTER: Fuchs CD 

PROVIDER: S-EPMC10568427 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature