Adaptive regulation of bile salt transporters in cholestasis - the role of MRPs

摘要

Bile salt transporters in the liver, kidney and intestine undergo adaptive regulation in response to cholestatic liver injury. These adaptations may minimize the retention of bile salts in the liver and thus attenuate liver injury. Both transcriptional and post-transcriptional changes occur after bile duct ligation in the rat, resulting in down-regulation of the sodium taurocholate cotransporting polypeptide, Ntcp and Oatp2 at the sinusoidal membrane of the hepatocyte and the sodium-dependent bile salt transporter in ileum and renal proximal tubule. In contrast the canalicular bile salt export pump, Bsep, while diminished, continues to be expressed, even though there is complete bile duct obstruction. Mrp2 at the apical membrane of the hepatocyte and proximal tubule are down- and up-regulated respectively1. In contrast, Mrp3 and Mrp4 are markedly up-regulated at the sinusoidal membrane of the hepatocytes but remain unchanged in the kidney (Mrp3) or are post-transcriptionally down-regulated (Mrp4).