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The gut in iron homeostasis: role of HIF-2 under normal and pathological conditions
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Although earlier, seminal studies demonstrated that the gut per se has the intrinsic ability to regulate the rates of iron absorption, the spotlight in the past decade has been placed on the systemic regulation of iron homeostasis by the hepatic hormone hepcidin and the molecular mechanisms that regulate its expression. Recently, however, attention has returned to the gut based on the finding that hypoxia inducible factor-2 (HIF-2α) regulates the expression of key genes that contribute to iron absorption. Here we review the current understanding of the molecular mechanisms that regulate iron homeostasis in the gut by focusing on the role of HIF-2 under physiological steady-state conditions and in the pathogenesis of iron-related diseases. We also discuss implications for adapting HIF-2–based therapeutic strategies in iron-related pathological conditions.
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“In the hypoxic duodenal environment, IRP1 controls translation of hypoxia-inducible factor 2α (HIF-2α) which, stabilized by prolyl hydroxylase, upregulates the expression of apical (DMT1) and basolateral (ferroportin) enterocyte iron transporters.62”
From Iron metabolism and iron disorders revisited in the hepcidin era (2020) · cites this paper as [62]
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Metadata
- Authors
- Mastrogiannaki, M., Matak, P., & Peyssonnaux, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Peyssonnaux, Carole
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2013-08-08
- Volume
- 122
- Issue
- 6
- Pages
- 885-892
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC3743464
- OpenAlex
- W2160602863
- Cited by
- 116
- References
- 102
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 8 · 2020: 10 · 2019: 4 · 2018: 13 · 2017: 7 · 2016: 8 · 2015: 17 · 2014: 6 · 2013: 4
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Physical Sciences › Materials Science › Metals and Alloys › Iron and Steelmaking Processes
- Keywords
- iron homeostasis, HIF-2α, HIF-2, hepcidin, iron-related diseases
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Animals, Hypoxia, Gene Expression Regulation, Hemochromatosis, Homeostasis, Humans, Inflammation, Iron, Male, Polycythemia, Enterocytes, Hepatocytes, Antimicrobial Cationic Peptides, Iron Regulatory Protein 1, Iron Regulatory Protein 2, Gastrointestinal Tract, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Hepcidins
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