Fig 2: Upregulation of CYP2B expression in DKO and PFIC5 livers. (A) Mouse liver sections from WT, DKO, QKO,Bsep+/-, andBsep-/- mice were stained with anti-BSEP (upper panel) and anti-CYP2B6 (lower panel) antibodies. Next, nuclei were counterstained with hematoxylin. Arrowheads indicate canalicular BSEP expression. (B) Cirrhotic liver sections from end-stage disease of patients with PFIC5 and PFIC2 were stained with anti-CYP2B6 antibody. (Inset) Parenchymal CYP2B6 staining. Arrowhead indicates positive CYP2B6 staining in a biliary tract.

Fig 3: TKO further attenuates ABCB11-mediated fecal BA excretion. (A) mRNA (n = 8) and (B) protein levels (n = 3) of ABCB11 were analyzed by q-PCR and proteomics, respectively. Ratio (%) indicates the proportion of ABCB11 expressions compared to WT. (C) Immunostaining of ABCB11 (magnification ×200); arrowhead, residual canalicular ABCB11 expression. (D) BA levels in gallbladder-collected bile (n = 4) and feces (n = 3). ANOVA followed by Tukey HSD, #P < 0.05, ###P < 0.005. Abbreviation: iFOT, intensity-based fraction of total.

Fig 4: TC treatment enhances canalicular and basolateral BA transporters. (A) Fecal BA excretion (n = 4) and urinary BA concentration (n = 3) in TC-treated (1 week) DKO and BKO. (B) mRNA levels of BA transporters (n = 4). (C) Immunostaining of ABCB11, ABCC3, and ABCC4 (magnification ×200). Arrowhead, positive area. Student t test; *P < 0.05, ***P < 0.005 compared to CO-treated group. Abbreviation: MDR, multidrug resistance.