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

Peyssonnaux C, Zinkernagel AS, Schuepbach RA, Rankin E, Vaulont S, Haase VH, Nizet V, Johnson RS
J Clin Invest. 2007 117 (7): 1926-32

PMID: 17557118 · PMCID: PMC1884690 · DOI:10.1172/JCI31370

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.

MeSH Terms (24)

Albumins Animals Antimicrobial Cationic Peptides Base Sequence Cation Transport Proteins Down-Regulation Gene Deletion Hepatocytes Hepcidins Homeostasis Humans Hypoxia-Inducible Factor 1 Integrases Iron Liver Mice Mice, Inbred C57BL Mice, Transgenic Molecular Sequence Data Polycythemia Promoter Regions, Genetic Protein Binding Up-Regulation Von Hippel-Lindau Tumor Suppressor Protein

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