Expression of hepatic transporters OATP-C and MRP2 in primary sclerosing cholangitis.
OBJECTIVE
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 beta-actin. PCR products were quantified densitometrically.


RESULTS
When normalized for beta-actin expression, the level of OATP-C mRNA in liver 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 controls (MRP2/beta-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.
Oswald
M
M
Department of Medicine II, Klinikum Grosshadern, University of Munich, 81377 Munich, Germany.
Kullak-Ublick
G A
GA
Paumgartner
G
G
Beuers
U
U
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D000368:Aged; D027321:Anion Transport Proteins; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D015209:Cholangitis, Sclerosing / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis
D018435:ATP Binding Cassette Transporter, Subfamily B; D027321:Anion Transport Proteins; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C000715087:ABCC2 protein, human; C421109:multidrug resistance-associated protein 1