Title
Down-regulation of OATP1B proteins correlates with hyperbilirubinemia in advanced cholestasis
Author
Sticova, E.
Lodererova, A.
van de Steeg, E.
Frankova, S.
Kollar, M.
Lanska, V.
Kotalova, R.
Dedic, T.
Schinkel, A.H.
Jirsa, M.
Publication year
2015
Abstract
Aim: Organic anion-transporting polypeptides OATP1B1 and OATP1B3 are sinusoidal membrane transporters mediating liver uptake of a wide range of substrates including conjugated and unconjugated bilirubin, xenobiotics and drugs. Absence of OATP1Bs in the liver causes Rotor syndrome. Our aim was to correlate OATP1B expression with hyperbilirubinemia in common liver diseases. Methods: Immunoreactivity of five antibodies against human OATP1Bs was tested on frozen and formalin-fixed paraffin-embedded liver tissue of mouse strains transgenic for SLCO1B1 or SLCO1B3 and on human specimens. The proportion of hepatocytes expressing OATP1Bs was then assessed immunohistologically in formalin-fixed paraffin-embedded liver samples obtained from patients with hepatocellular and primary biliary liver diseases. UGT1A1 promoter TATA-box and SLCO1B1 rs4149056 genotyping was performed to rule out individuals predisposed to hyperbilirubinemia. Results: The most specific detection of OATP1B3 was achieved with the H-52 (sc-98981) antibody. OATP1B1 was specifically recognized with the ESL (ab15441) anti-OATP1B1 antibody, but only in frozen sections. The MDQ (ab15442) anti-OATP1B1 antibody cross-reacted with both OATP1B proteins in liver tissue of the transgenic mouse strains. Expression of the OATP1B proteins was decreased in advanced liver diseases and inversely correlated with serum bilirubin levels. The reduction was more pronounced in advanced primary biliary diseases (1.9±1.1 vs. 2.7±0.6; P=0.009). Conclusions: Down-regulation of OATP1B proteins may contribute to pathogenesis of jaundice accompanying advanced cholestatic liver diseases.
Subject
ELSS - Earth, Life and Social Sciences
Life
Healthy Living
Biomedical Innovation
Bilirubin
Cholestasis
Immunohistochemistry
Liver disease
Organic anion transporter
MSB - Microbiology and Systems Biology
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TNO identifier
527763
ISSN
1936-2625
Source
International Journal of Clinical and Experimental Pathology, 8 (8), 5252-5262
Document type
article