Expression of hepatic transporters OATP-C and MRP2 in primary sclerosing cholangitis

Background/Aims: In chronic cholestatic liver diseases, biliary excretion o f organic anions from blood into bile is impaired. The aim of this study wa s to identify the underlying mechanism. Methods: Expression of the basolate ral organic anion transporting polypeptide OATP-C (SLC21A6) and the canalic ular multidrug resistance protein 2 (MRP2) was studied in patients with pri mary sclerosing cholangitis (PSC) (n=4), a chronic cholestatic liver diseas e, and in non-cholestatic controls (n=4) (two with chronic hepatitis C, one with idiopathic liver cirrhosis and one with fatty liver). Total RNA was i solated from liver tissue, reverse transcribed and subjected to polymerase chain reaction (PCR) amplification using primers specific for OATP-C, MRP2 and beta -actin. PCR products were quantified densitometrically. Results: W hen normalized for beta -actin expression, the level of OATP-C mRNA in live r tissue of patients with PSC was 49% of controls (OATP-C/beta -actin 1.60/-0.25 vs. 3.24+/-0.69, p<0.05) and the level of MRP2 mRNA was 27% of contr ols (MRP2/<beta>-actin 0.70+/-0.36 vs. 2.54+/-0.56;p<0.01). Conclusions: Bo th OATP-C and MRP2 are decreased as measured by mRNA level in PSC. Downregu lation of OATP-C might be the consequence of impaired canalicular secretion of organic anions and could serve to reduce the organic anion load of chol estatic hepatocytes.