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    Transferrin receptor 2 is crucial for iron sensing in human hepatocytes

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    Authors
    Rapisarda, Chiara
    Puppi, Juliana
    Hughes, Robin D.
    Dhawan, Anil
    Farnaud, Sébastien
    Evans, Robert W.
    Sharp, Paul A.
    Issue Date
    2010-06-24
    Subjects
    transferrin
    hepcidins
    iron deficiency
    hepatocytes
    
    Metadata
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    Abstract
    Hepcidin expression in vivo is regulated in proportion to iron status (i.e., increased by iron loading and decreased in iron deficiency). However, in vitro studies with hepatoma cell lines often show an inverse relationship between iron status and hepcidin expression. Here, we investigated possible molecular mechanisms responsible for the differences in iron sensing between hepatoma cell lines and human primary hepatocytes. RNA was collected from primary human hepatocytes, and HepG2 and HuH7 hepatoma cells were treated with either transferrin-bound and non-transferrin-bound iron. Expression of hepcidin, transferrin receptor 2, HFE, and hemojuvelin were quantified by real-time PCR. Hepcidin expression was increased in primary human hepatocytes following 24-h exposure to holoferric transferrin. In contrast, hepcidin mRNA levels in hepatoma cells were decreased by transferrin. Hepcidin expression was positively correlated with transferrin receptor 2 mRNA levels in primary human hepatocytes. Compared with primary hepatocytes, transferrin receptor 2 expression was significantly lower in hepatoma cell lines; furthermore, there was no correlation between transferrin receptor 2 and hepcidin mRNA levels in either HepG2 or HuH7 cells. Taken together our data suggest that transferrin receptor 2 is a likely candidate to explain the differences in iron sensing between hepatoma cell lines and primary human hepatocytes.
    Citation
    Rapisarda, C. et al (2010) 'Transferrin receptor 2 is crucial for iron sensing in human hepatocytes' AJP: Gastrointestinal and Liver Physiology 299 (3):G778
    Publisher
    American Physiological Society
    Journal
    AJP: Gastrointestinal and Liver Physiology
    URI
    http://hdl.handle.net/10547/593507
    DOI
    10.1152/ajpgi.00157.2010
    PubMed ID
    20576915
    PubMed Central ID
    PMC2950680
    Additional Links
    http://ajpgi.physiology.org/cgi/doi/10.1152/ajpgi.00157.2010
    http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20576915/
    Type
    Article
    Language
    en
    ISSN
    0193-1857
    1522-1547
    ae974a485f413a2113503eed53cd6c53
    10.1152/ajpgi.00157.2010
    Scopus Count
    Collections
    Cell and Cryobiology Research Group

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