Adaptive hepatobiliary transporter regulation by ursodeoxycholic acid

摘要

Cholestasis is associated with impaired expression and function of hepatic uptake (Ntcp/SlclOal, Oatp/SIc21a) and excretory systems (Bsep/Abcbll, Mrp2/Abcc2) for bile acids and other organic anions in rodents, changes which may maintain and contribute to cholestasis. Moreover, adaptive transporter changes such as induction of alternative efflux pumps in liver (Mrp3/Abcc3, Mrp4/Abcc4) and kidney (Mrp2, Mrp4) may help to limit hepatic accumulation of potentially toxic biliary constituents in cholestasis by providing alternative escape routes. In line with these observations in rodent models of cholestasis, similar findings (down-regulation of NTCP, 0ATP2/0ATP-C/ SLC21A6; induction of MRP3, MRP4) have been obtained in livers from patients with cholestatic liver diseases (e.g. PBO).