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    Quantitative and qualitative alterations of heparan sulfate in fibrogenic liver diseases and hepatocellular cancer.

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    Authors
    Tátrai, Péter
    Egedi, Krisztina
    Somorácz, Aron
    Van Kuppevelt, Toin H
    Ten Dam, Gerdy
    Lyon, Malcolm
    Deakin, Jon A
    Kiss, András
    Schaff, Zsuzsa
    Kovalszky, Ilona
    Affiliation
    Second Department of Pathology, Semmelweis University, 93 Ulloi út H-1091 Budapest, Hungary. peter.tatrai@biomembrane.hu
    Issue Date
    2010-05
    
    Metadata
    Show full item record
    Abstract
    Heparan sulfate (HS), due to its ability to interact with a multitude of HS-binding factors, is involved in a variety of physiological and pathological processes. Remarkably diverse fine structure of HS, shaped by non-exhaustive enzymatic modifications, influences the interaction of HS with its partners. Here we characterized the HS profile of normal human and rat liver, as well as alterations of HS related to liver fibrogenesis and carcinogenesis, by using sulfation-specific antibodies. The HS immunopattern was compared with the immunolocalization of selected HS proteoglycans. HS samples from normal liver and hepatocellular carcinoma (HCC) were subjected to disaccharide analysis. Expression changes of nine HS-modifying enzymes in human fibrogenic diseases and HCC were measured by quantitative RT-PCR. Increased abundance and altered immunolocalization of HS was paralleled by elevated mRNA levels of HS-modifying enzymes in the diseased liver. The strong immunoreactivity of the normal liver for 3-O-sulfated epitope further increased with disease, along with upregulation of 3-OST-1. Modest 6-O-undersulfation of HCC HS is probably explained by Sulf overexpression. Our results may prompt further investigation of the role of highly 3-O-sulfated and partially 6-O-desulfated HS in pathological processes such as hepatitis virus entry and aberrant growth factor signaling in fibrogenic liver diseases and HCC.
    Citation
    Quantitative and qualitative alterations of heparan sulfate in fibrogenic liver diseases and hepatocellular cancer. 2010, 58 (5):429-41 J. Histochem. Cytochem.
    Journal
    The Journal of Histochemistry and Cytochemistry
    URI
    http://hdl.handle.net/10541/109396
    DOI
    10.1369/jhc.2010.955161
    PubMed ID
    20124094
    Type
    Article
    Language
    en
    ISSN
    1551-5044
    ae974a485f413a2113503eed53cd6c53
    10.1369/jhc.2010.955161
    Scopus Count
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    All Paterson Institute for Cancer Research

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