ArticleThe Journal of clinical investigation2009
HIF-2alpha, but not HIF-1alpha, promotes iron absorption in mice.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 275 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
275 citing papers in PubMed, 3 syntheses or guidelines pooled it, 490 citations in OpenAlex.
- Efficacy of daprodustat for patients on dialysis with anemia: systematic review and network meta-analysis.The Pan African medical journal · 2024Pooled it
- Recommendations by the Asian Pacific society of nephrology (APSN) on the appropriate use of HIF-PH inhibitors.Nephrology (Carlton, Vic.) · 2021Guideline
- Effect of hypoxia-inducible factor-prolyl hydroxylase inhibitors on anemia in patients with CKD: a meta-analysis of randomized controlled trials including 2804 patients.Renal failure · 2020Pooled it
- A preliminary study of roxadustat in the treatment of aplastic anemia patients with inadequate erythroid responses.Annals of hematology · 2024Trial
- The benefits of iron supplementation following blood donation vary with baseline iron status.American journal of hematology · 2020Trial
- Trial
- Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia.Journal of the American Society of Nephrology : JASN · 2016Trial
- The role of iron in normal and impaired testicular function.Andrology · 2026Review
- Obesity and Iron Metabolism: Mechanisms, Status Assessment, and Clinical Implications.Current obesity reports · 2026Review
- Precision dietary strategies for enriching animal-derived foods with antioxidants and omega-3 fatty acids.Veterinary and animal science · 2026Review
- Review
- Synergistic Contribution of HFE H63D Mutation to Secondary Polycythemia Pathogenesis at Moderate-High Altitude: A Retrospective Cohort Study.Diagnostics (Basel, Switzerland) · 2026Article
- Overlaps in mammalian iron and manganese homeostasis: recent advances.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Unveiling melatonin's multifaceted actions against ferroptotic neurotoxicity in ischemic stroke.Toxicology reports · 2026Review
- HIF-2α could be a key regulator of Fe homeostasis in the gut of yellow-feathered broilers.Poultry science · 2026Article
- High‑altitude polycythemia: Unveiling the molecular landscape beyond erythropoietin (Review).International journal of molecular medicine · 2026Review
- Review
- Labile iron pool dynamics do not drive ferroptosis in colorectal cancer cells.The Journal of biological chemistry · 2026Article
- Navigating Anemia Therapy in CKD With Hypoxia-Inducible Factor Activators: A Review.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2026Review
- Article
215 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HIF transcription factors (HIF-1 and HIF-2) are central mediators of cellular adaptation to hypoxia. Because the resting partial pressure of oxygen is low in the intestinal lumen, epithelial cells are believed to be mildly hypoxic. Having recently established a link between HIF and the iron-regulatory hormone hepcidin, we hypothesized that HIFs, stabilized in the hypoxic intestinal epithelium, may also play critical roles in regulating intestinal iron absorption. To explore this idea, we first established that the mouse duodenum, the site of iron absorption in the intestine, is hypoxic and generated conditional knockout mice that lacked either Hif1a or Hif2a specifically in the intestinal epithelium. Using these mice, we found that HIF-1alpha was not necessary for iron absorption, whereas HIF-2alpha played a crucial role in maintaining iron balance in the organism by directly regulating the transcription of the gene encoding divalent metal transporter 1 (DMT1), the principal intestinal iron transporter. Specific deletion of Hif2a led to a decrease in serum and liver iron levels and a marked decrease in liver hepcidin expression, indicating the involvement of an induced systemic response to counteract the iron deficiency. This finding may provide a basis for the development of new strategies, specifically in targeting HIF-2alpha, to improve iron homeostasis in patients with iron disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.