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

Authors


Ulrich Beuers, Medizinische Klinik II, Klinikum Großhadern, Marchioninistrasse 15, D-81377 München, Germany. Tel: 49 89 7095 3129.
Fax: 49 89 7095 8887.
e-mail: beuers@med2.med.uni-muenchen.de

Abstract

Abstract:Background/Aims: In chronic cholestatic liver diseases, biliary excretion of organic anions from blood into bile is impaired. The aim of this study was to identify the underlying mechanism. Methods: Expression of the basolateral organic anion transporting polypeptide OATP-C (SLC21A6) and the canalicular multidrug resistance protein 2 (MRP2) was studied in patients with primary sclerosing cholangitis (PSC) (n=4), a chronic cholestatic liver disease, 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 isolated from liver tissue, reverse transcribed and subjected to polymerase chain reaction (PCR) amplification using primers specific for OATP-C, MRP2 and β-actin. PCR products were quantified densitometrically. Results: When normalized for β-actin expression, the level of OATP-C mRNA in liver tissue of patients with PSC was 49% of controls (OATP-C/β-actin 1.60±0.25 vs. 3.24±0.69; p<0.05) and the level of MRP2 mRNA was 27% of controls (MRP2/β-actin 0.70±0.36 vs. 2.54±0.56; p<0.01). Conclusions: Both OATP-C and MRP2 are decreased as measured by mRNA level in PSC. Downregulation of OATP-C might be the consequence of impaired canalicular secretion of organic anions and could serve to reduce the organic anion load of cholestatic hepatocytes.

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