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PMID: 17557118 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

The Journal of clinical investigation ·Vol. 117 ·No. 7 ·2007-07-00 ·Pages 1926-32

Peyssonnaux C, Zinkernagel AS, Schuepbach RA, Rankin E, Vaulont S, Haase VH, Nizet V, Johnson RS

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.

MeSH Terms
Albumins/genetics,metabolism Animals Antimicrobial Cationic Peptides/genetics,metabolism Base Sequence Cation Transport Proteins/metabolism Down-Regulation Gene Deletion Hepatocytes/drug effects,metabolism Hepcidins Homeostasis/drug effects Humans Hypoxia-Inducible Factor 1/deficiency,genetics,metabolism Integrases/genetics,metabolism Iron/pharmacology Liver/metabolism Mice Mice, Inbred C57BL Mice, Transgenic Molecular Sequence Data Polycythemia/genetics,metabolism,pathology Promoter Regions, Genetic/genetics Protein Binding Up-Regulation Von Hippel-Lindau Tumor Suppressor Protein/genetics,metabolism
Chemicals
Albumins Antimicrobial Cationic Peptides Cation Transport Proteins HAMP protein, human Hamp protein, mouse Hepcidins Hypoxia-Inducible Factor 1 metal transporting protein 1 Iron Von Hippel-Lindau Tumor Suppressor Protein Cre recombinase Integrases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Peyssonnaux Carole
Molecular Biology Section, Division of Biological Sciences, UCSD School of Medicine, La Jolla, CA 92093-0377, USA.
Zinkernagel Annelies S
Schuepbach Reto A
Rankin Erinn
Vaulont Sophie
Haase Volker H
Nizet Victor
Johnson Randall S
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI31370
Published
2007-07-00
Pages
1926-32
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1884690
Subset
IM
Grants
NIAID NIH HHS · R01 AI060840 · United States
NCI NIH HHS · R01 CA100787 · United States
NIDDK NIH HHS · R21 DK073467 · United States
NIAID NIH HHS · AI060840 · United States
External Links
PubMed source DOI: 10.1172/JCI31370 PMC Full Text View journal details
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