ArticleHaematologica2012
Hepatic hypoxia-inducible factor-2 down-regulates hepcidin expression in mice through an erythropoietin-mediated increase in erythropoiesis.
Article in Haematologica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- Recommendations by the Asian Pacific society of nephrology (APSN) on the appropriate use of HIF-PH inhibitors.Nephrology (Carlton, Vic.) · 2021Guideline
- Maternal iron kinetics and maternal-fetal iron transfer in normal-weight and overweight pregnancy.The American journal of clinical nutrition · 2022Trial
- 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
- Gut microbiota and iron deficiency anemia: Mechanisms, microbial signatures, and dietary interactions (A narrative review).Asia Pacific journal of clinical nutrition · 2026Review
- 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
- Impaired iron balance and erythrocytosis: a complex relationship.Blood cancer journal · 2026Review
- Ferroptosis in cardiovascular diseases: molecular mechanisms and a novel therapeutic target.Molecular biomedicine · 2026Review
- Iron: Regulation, redox homeostasis, and ferroptosis in cancer.Ferroptosis and oxidative stress · 2026Article
- Chronic inflammation is not associated with attenuated sodium-glucose co-transporter 2 inhibitor-induced hemoglobin increase in patients with diabetes.Journal of diabetes investigation · 2026Article
- Advances in the characterization of in vitro-generated red blood cells: from biophysical properties to functional applications.Stem cell research & therapy · 2025Review
- Iron metabolism in rheumatic diseases.Journal of translational autoimmunity · 2025Review
- Mathematical modeling reveals ferritin as the strongest cellular driver of dietary iron transfer block in enterocytes.PLoS computational biology · 2025Article
- Exosome-based modulation of ferroptosis in neurological disorders: mechanisms, therapeutic potential, and translational challenges.Frontiers in immunology · 2025Review
- Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects.Signal transduction and targeted therapy · 2024Review
- Article
- Mechanisms controlling cellular and systemic iron homeostasis.Nature reviews. Molecular cell biology · 2024Review
- Hypoxia-Induced Signaling in Gut and Liver Pathobiology.Annual review of pathology · 2024Review
- The role and clinical implications of HIF-PHI daprodustat in dialysis-dependent and non-dialysis-dependent chronic kidney disease anemic patients: a general review.Frontiers in nephrology · 2024Review
- Iron Status and Physical Performance in Athletes.Life (Basel, Switzerland) · 2023Review
- Drugs activating hypoxia-inducible factors correct erythropoiesis and hepcidin levels via renal EPO induction in mice.Blood advances · 2023Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIron metabolism, regulated by the iron hormone hepcidin, and oxygen homeostasis, dependent on hypoxia-inducible factors, are strongly interconnected. We previously reported that in mice in which both liver hypoxia-inducible factors-1 and -2 are stabilized (the hepatocyte von Hippel-Lindau knockout mouse model), hepcidin expression was strongly repressed and we hypothesized that hypoxia-inducible factor-2 could be the major regulatory component contributing to the hepcidin down-regulation. DESIGN AND
methodsWe generated and analyzed hepatocyte-specific knockout mice harboring either hypoxia-inducible factor-2α deficiency (Hif2a knockout) or constitutive hypoxia-inducible factor-2α stabilization (Vhlh/Hif1a knockout) and ex vivo systems (primary hepatocyte cultures). Hif2a knockout mice were fed an iron-deficient diet for 2 months and Vhlh/Hif1a knockout mice were treated with neutralizing erythropoietin antibody.
resultsWe demonstrated that hypoxia-inducible factor-2 is dispensable in hepcidin gene regulation in the context of an adaptive response to iron-deficiency anemia. However, its overexpression in the double Vhlh/Hif1a hepatocyte-specific knockout mice indirectly down-regulates hepcidin expression through increased erythropoiesis and erythropoietin production. Experiments in primary hepatocytes confirmed the non-autonomous role of hypoxia-inducible factor-2 in hepcidin regulation.
conclusionsWhile our results indicate that hypoxia-inducible factor-2 is not directly involved in hepcidin repression, they highlight the contribution of hepatic hypoxia-inducible factor-2 to the repression of hepcidin through erythropoietin-mediated increased erythropoiesis, a result of potential clinical interest.
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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.