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Transferrin receptor 2 is crucial for iron sensing in human hepatocytes

  • Sebastien Farnaud
    ,
  • Chiara Rapisarda
    ,
  • Juliana Puppi
    ,
  • Robin D. Hughes
    ,
  • Anil Dhawan
    ,
  • Robert W. Evans
  • King's College London
    ,
  • Brunel University London
Research Output: Contribution to journal Article Peer-review

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.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages G778

Journal (Volume, Issue Number)

American Journal of Physiology - Gastrointestinal and Liver Physiology (Volume 299, Issue 3)

Publication milestones

  • Published - 24/06/2010

Publication status

Published - 24/06/2010

ISSN

0193-1857

External Publication IDs

  • handle.net: 10547/593507
  • Scopus: 77956998439

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