ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Activation of Intestinal HIF2α Ameliorates Iron-Refractory Anemia.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- Chronic Cerebral Hypoxia and Cognitive Impairment: A Systematic Review and Meta-Analysis Based on Chronic Mountain Sickness, Anemia, Chronic Obstructive Pulmonary Disease, and Obstructive Sleep Apnea.CNS neuroscience & therapeutics · 2026Pooled it
- Proteomic profiling of cephalic vein reveals potential biomarkers for arteriovenous fistula neointimal hyperplasia in ESRD patients.Renal failure · 2026Article
- Animal models of anemia of inflammation: Methodological advances, limitations, and translational applications.Animal models and experimental medicine · 2026Review
- Resveratrol-activated PI3K/AKT/mTOR signaling pathway attenuates ferroptosis by promoting NRF2/GPX4 metabolic pathway to mitigate IFN-gamma-mediated aplastic anemia.Chinese medicine · 2026Article
- Vitamin B6 deficiency anemia resembles iron-deficiency anemia but does not activate intestinal HIF2⍺.Experimental hematology · 2026Article
- <p>Prolyl hydroxylase domain proteins: Localization, regulation, function and their role in erythropoiesis (Review)</p>.Molecular medicine reports · 2026Review
- USP10 regulates HIF2α stability by deubiquitinating HIF2α regardless ofTranslational andrology and urology · 2026Article
- Targeting hepcidin to restore oral iron efficacy after vertical sleeve gastrectomy.Frontiers in nutrition · 2026Article
- Iron metabolism and ferroptosis in human health and disease.BMC biology · 2025Review
- Ferrostatin-1 reduces the inflammatory response of rheumatoid arthritis by decreasing the antigen presenting function of fibroblast-like synoviocytes.Journal of translational medicine · 2025Article
- Dietary Iron Absorption: Biochemical and Nutritional Aspects.Advances in experimental medicine and biology · 2025Review
- Activation of Intestinal HIF2α Ameliorates Iron-Refractory Anemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
In clinics, hepcidin levels are elevated in various anemia-related conditions, particularly in iron-refractory anemia and in high inflammatory states that suppress iron absorption, which remains an urgent unmet medical need. To identify effective treatment options for various types of iron-refractory anemia, the potential effect of hypoxia and pharmacologically-mimetic drug FG-4592 (Roxadustat) are evaluated, a hypoxia-inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitor, on mouse models of iron-refractory iron-deficiency anemia (IRIDA), anemia of inflammation and 5-fluorouracil-induced chemotherapy-related anemia. The potent protective effects of both hypoxia and FG-4592 on IRIDA as well as other 2 tested mouse cohorts are found. Mechanistically, it is demonstrated that hypoxia or FG-4592 could stabilize duodenal Hif2α, leading to the activation of Fpn transcription regardless of hepcidin levels, which in turn results in increased intestinal iron absorption and the amelioration of hepcidin-activated anemias. Moreover, duodenal Hif2α overexpression fully rescues phenotypes of Tmprss6 knockout mice, and Hif2α knockout in the gut significantly delays the recovery from 5-fluorouracil-induced anemia, which can not be rescued by FG-4592 treatment. Taken together, the findings of this study provide compelling evidence that targeting intestinal hypoxia-related pathways can serve as a potential therapeutic strategy for treating a broad spectrum of anemia, especially iron refractory anemia.
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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.