Transcriptomic analysis of a mouse model of intrahepatic cholestasis
The Farnesoid X receptor (FXR), is the main bile acids sensor expressed in hepatocytes. Obeticholic acid (OCA), a fairly potent FXR agonist, has been approved for the treatment of UDCA-resistant PBC, but FXR gene ablation protects against liver injury in cholestatic modes. The use of OCA causes itching in a substantial proportion of PBC patients, and at the dose 5 mg/d, has been linked to a cluster of severe liver injury, in some cases fatal, in PBC patients with decompensated cirrhosis and Child-Pugh Class B/C. To further elucidate the role of FXR in the pathogenesis of cholestasis, we have tested the obeticholic acid alone or in combination with a FXR antagonist, named as GP7, in a mouse model of ANIT (α-naphthylisothiocyanate) induced cholestasis. OCA and GP7 intrahepatic effect were evaluated by RNAseq analysis performed on Ion S5 Sequencer with Torrent Suite Software v6.