ArticleThe Journal of clinical investigation2019
Hepatic hepcidin/intestinal HIF-2α axis maintains iron absorption during iron deficiency and overload.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 3 of them syntheses that pooled it.
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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.
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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
122 citing papers in PubMed, 3 syntheses or guidelines pooled it, 197 citations in OpenAlex.
- Iron oxide nanoparticles carried by probiotics for iron absorption: a systematic review.Journal of nanobiotechnology · 2023Pooled it
- Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease.The Cochrane database of systematic reviews · 2022Pooled it
- A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.Communications biology · 2021Pooled it
- Effect of roxadustat on iron metabolism in patients with peritoneal dialysis: a real-world 24-week study.European journal of medical research · 2023Trial
- Iron-addicted colorectal cancers exploit heme-complex II axis to resist oxidative cell death.Cell metabolism · 2026Article
- HIF-2α could be a key regulator of Fe homeostasis in the gut of yellow-feathered broilers.Poultry science · 2026Article
- Identification and characterization of novel hepcidin mimetics that modulate ferroportin function.Blood red cells & iron · 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
- High‑altitude polycythemia: Unveiling the molecular landscape beyond erythropoietin (Review).International journal of molecular medicine · 2026Review
- Metal ions in aging and ocular diseases: biology, pathophysiology, and therapeutic strategies.npj aging · 2026Review
- Vitamin B6 deficiency anemia resembles iron-deficiency anemia but does not activate intestinal HIF2⍺.Experimental hematology · 2026Article
- The crosstalk between iron metabolism and immune tolerance in autoimmunity.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Article
- IRP1 deficiency alters mitochondrial metabolism and protects against metabolic syndrome pathologies.JCI insight · 2026Article
- Intestine-Specific Ferroportin Ablation Rescues from Systemic Iron Overload in Mice.Nutrients · 2026Article
- Iron: Regulation, redox homeostasis, and ferroptosis in cancer.Ferroptosis and oxidative stress · 2026Article
- Current research on the HIF-2α-EPO-Hb axis in hypoxic environments: from molecular mechanisms to clinical.Frontiers in medicine · 2026Review
- Association of gut microbiome signatures with iron metabolism response to roxadustat in peritoneal dialysis patients with anemia: a cross-sectional study.Frontiers in pharmacology · 2026Article
- The role of gut microbiota mediated ferroptosis in PCOS and the therapeutic potential of Chinese herbal medicine.Frontiers in medicine · 2026Review
- Targeting hepcidin to restore oral iron efficacy after vertical sleeve gastrectomy.Frontiers in nutrition · 2026Article
62 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Iron-related disorders are among the most prevalent diseases worldwide. Systemic iron homeostasis requires hepcidin, a liver-derived hormone that controls iron mobilization through its molecular target ferroportin (FPN), the only known mammalian iron exporter. This pathway is perturbed in diseases that cause iron overload. Additionally, intestinal HIF-2α is essential for the local absorptive response to systemic iron deficiency and iron overload. Our data demonstrate a hetero-tissue crosstalk mechanism, whereby hepatic hepcidin regulated intestinal HIF-2α in iron deficiency, anemia, and iron overload. We show that FPN controlled cell-autonomous iron efflux to stabilize and activate HIF-2α by regulating the activity of iron-dependent intestinal prolyl hydroxylase domain enzymes. Pharmacological blockade of HIF-2α using a clinically relevant and highly specific inhibitor successfully treated iron overload in a mouse model. These findings demonstrate a molecular link between hepatic hepcidin and intestinal HIF-2α that controls physiological iron uptake and drives iron hyperabsorption during iron overload.
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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.