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PMID: 19147412 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency.

Cell metabolism ·Vol. 9 ·No. 2 ·2009-02-00 ·Pages 152-64

Shah YM, Matsubara T, Ito S, Yim SH, Gonzalez FJ

Abstract

Iron deficiency and iron overload are among the most prevalent nutritional disorders worldwide. Duodenal cytochrome b (DcytB) and divalent metal transporter 1 (DMT1) are regulators of iron absorption. Their expression is increased during high systemic requirements for iron, but the molecular mechanisms that regulate DcytB and DMT1 expression are undefined. Hypoxia-inducible factor (HIF) signaling was induced in the intestine following acute iron deficiency in the duodenum, resulting in activation of DcytB and DMT1 expression and an increase in iron uptake. DcytB and DMT1 were demonstrated as direct HIF-2alpha target genes. Genetic disruption of HIF signaling in the intestine abolished the adaptive induction of iron absorption following iron deficiency, resulting in low systemic iron and hematological defects. These results demonstrate that HIF signaling in the intestine is a critical regulator of systemic iron homeostasis.

MeSH Terms
Animals Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism Basic Helix-Loop-Helix Transcription Factors/metabolism Cation Transport Proteins/metabolism Cytochrome b Group/metabolism Duodenum/metabolism Hypoxia-Inducible Factor 1/metabolism Hypoxia-Inducible Factor 1, alpha Subunit/metabolism Iron/metabolism Iron Deficiencies Mice Mice, Inbred C57BL Mice, Transgenic Oxidoreductases/metabolism Signal Transduction
Chemicals
Basic Helix-Loop-Helix Transcription Factors Cation Transport Proteins Cytochrome b Group Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2 Aryl Hydrocarbon Receptor Nuclear Translocator endothelial PAS domain-containing protein 1 Iron Oxidoreductases CYBRD1 protein, human
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Shah Yatrik M
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Matsubara Tsutomu
Ito Shinji
Yim Sun-Hee
Gonzalez Frank J
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Article Info
Journal
Cell metabolism
Abbr.
Cell Metab
ISSN
1932-7420
DOI
10.1016/j.cmet.2008.12.012
Published
2009-02-00
Epub
2009-00-15
Pages
152-64
Language
English
Region
United States
NLM ID
101233170
PMCID
PMC2659630
Subset
IM
Grants
Intramural NIH HHS · Z01 BC005561-20 · United States
External Links
PubMed source DOI: 10.1016/j.cmet.2008.12.012 PMC Full Text View journal details
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