Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs)
Carole Peyssonnaux, … , Victor Nizet, Randall S. Johnson
Carole Peyssonnaux, … , Victor Nizet, Randall S. Johnson
Published July 2, 2007
Citation Information: J Clin Invest. 2007;117(7):1926-1932. https://doi.org/10.1172/JCI31370.
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Research Article

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

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.

Authors

Carole Peyssonnaux, Annelies S. Zinkernagel, Reto A. Schuepbach, Erinn Rankin, Sophie Vaulont, Volker H. Haase, Victor Nizet, Randall S. Johnson

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Figure 1

Iron deficiency downregulates hepcidin in an HIF-1–dependent fashion.

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Iron deficiency downregulates hepcidin in an HIF-1–dependent fashion. ...
(A) Hepcidin mRNA level in livers of WT mice under regular or low-iron diet (3 weeks), determined by real-time RT-PCR. Results, normalized to 18S ribosomal RNA expression, are expressed as mean ± SD (n = 5 in each group). (B) HIF-1 expression in liver extracts of iron-starved WT mice by Western blotting. (C) Hepcidin mRNA expression in livers of WT and Albumin-Cre/HIF-1αflox/flox (HIF-1–/–) iron-starved mice by real-time RT-PCR (n = 8).