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J Clin Invest. 2007 Jul;117(7):1926-32.

Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs).

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1
Molecular Biology Section, Division of Biological Sciences, UCSD School of Medicine, La Jolla, CA 92093-0377, USA.

Abstract

Iron is essential for many biological processes, including oxygen delivery, and its supply is tightly regulated. Hepcidin, a small peptide synthesized in the liver, is a key regulator of iron absorption and homeostasis in mammals. Hepcidin production is increased by iron overload and decreased by anemia and hypoxia; but the molecular mechanisms that govern the hepcidin response to these stimuli are not known. Here we establish that the von Hippel-Lindau/hypoxia-inducible transcription factor (VHL/HIF) pathway is an essential link between iron homeostasis and hepcidin regulation in vivo. Through coordinate downregulation of hepcidin and upregulation of erythropoietin and ferroportin, the VHL-HIF pathway mobilizes iron to support erythrocyte production.

PMID:
17557118
PMCID:
PMC1884690
DOI:
10.1172/JCI31370
[Indexed for MEDLINE]
Free PMC Article
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