Transferrin receptor 2 is crucial for iron sensing in human hepatocytes
Authors
Rapisarda, ChiaraPuppi, Juliana
Hughes, Robin D.
Dhawan, Anil
Farnaud, Sébastien
Evans, Robert W.
Sharp, Paul A.
Issue Date
2010-06-24
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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):G778Publisher
American Physiological SocietyPubMed ID
20576915PubMed Central ID
PMC2950680Additional Links
http://ajpgi.physiology.org/cgi/doi/10.1152/ajpgi.00157.2010http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20576915/
Type
ArticleLanguage
enISSN
0193-18571522-1547
ae974a485f413a2113503eed53cd6c53
10.1152/ajpgi.00157.2010
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