PDZK1 gene transfer ameliorates lipopolysaccharide-induced cholestasis in rats by rescuing hepatic ABC transporters.

Lipopolysaccharide (LPS) causes inflammatory cholestasis in sepsis. We investigated the role of PDZK1 in the repression of ABC transporters in LPS-induced cholestasis. Lentiviral gene transfer of PDZK1 to rats was conducted to explore its influence on cholestasis induced by LPS. And the effect of lentivirus-mediated shRNA targeting PDZK1 on ABC transporters in rat liver BRL-3A cells was evaluated. Lentiviral vector encoding rat PDZK1 was administered to rats by tail intravenous injection. Obviously elevated serum total bile acid level and liver biochemical markers in cholestatic rats were decreased by the Lv-PDZK1 delivery. Also, Lv-PDZK1 delivery stimulated the suppressed hepatic ABC transporters expression. In vitro, after the lentiviral vector LV3/PDZK1 shRNA transfection, no expression of PDZK1 and mild expression of ABC transporters were detected in BRL-3A cells by Western blotting. Our results indicate that the lentiviral-mediated hepatocyte PDZK1 expression ameliorates LPS-induced cholestasis in rats by rescuing hepatic ABC transporters expression.