ArticleGastroenterology2011
Hypoxia-inducible factor-2α mediates the adaptive increase of intestinal ferroportin during iron deficiency in mice.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers, 1 of them a synthesis that pooled it.
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Who cites it
173 citing papers in PubMed, 1 synthesis or guideline pooled it, 256 citations in OpenAlex.
- Recommendations by the Asian Pacific society of nephrology (APSN) on the appropriate use of HIF-PH inhibitors.Nephrology (Carlton, Vic.) · 2021Guideline
- A preliminary study of roxadustat in the treatment of aplastic anemia patients with inadequate erythroid responses.Annals of hematology · 2024Trial
- Trial
- Iron Prevents Hypoxia-Associated Inflammation Through the Regulation of Nuclear Factor-κB in the Intestinal Epithelium.Cellular and molecular gastroenterology and hepatology · 2019Trial
- Placental Iron Homeostasis: Navigating the Delicate Balance Between Transport and Ferroptosis.International journal of molecular sciences · 2026Review
- Ferroportin at the Crossroads of Iron Biology: Disease, Regulation and Modulation.Biomolecules · 2026Review
- Unveiling melatonin's multifaceted actions against ferroptotic neurotoxicity in ischemic stroke.Toxicology reports · 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
- 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
- Vitamin B6 deficiency anemia resembles iron-deficiency anemia but does not activate intestinal HIF2⍺.Experimental hematology · 2026Article
- Uric Acid Induces Hepatocytes Ferroptosis Through HIF-2α/DMT1-Mediated Iron Overload.International journal of molecular sciences · 2026Article
- Intestine-Specific Ferroportin Ablation Rescues from Systemic Iron Overload in Mice.Nutrients · 2026Article
- Hepatocyte HIF2α Downregulates the Urea Cycle Through Suppression of HNF4α.Gastro hep advances · 2026Article
- Targeting hepcidin to restore oral iron efficacy after vertical sleeve gastrectomy.Frontiers in nutrition · 2026Article
- Acute kidney injury and iron metabolism: A narrative review focusing on pathophysiology and therapy.Smart molecules : open access · 2025Review
- Iron Stress Reprograms Enterocyte Metabolism.Metabolites · 2025Article
- Crosstalk Between Microbiome and Ferroptosis in Diseases: From Mechanism to Therapy.Comprehensive Physiology · 2025Review
- Oxygen and immunity toInfection and immunity · 2025Review
- Iron at the crossroads of host-microbiome interactions in health and disease.Nature microbiology · 2025Review
- Downregulation of ferroptosis-related Genes can regulate the invasion and migration of osteosarcoma cells.Scientific reports · 2025Article
113 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsIron deficiency and iron overload affect over a billion people worldwide. Dietary iron absorption in the small intestine is required for systemic iron homeostasis. Ferroportin (FPN) is the only characterized, mammalian, basolateral iron exporter. Despite the importance of FPN in maintaining iron homeostasis, its in vivo mechanisms of regulation are unclear.
methodsSystemic iron homeostasis was assessed in mice with intestine-specific disruption of genes encoding the von Hippel-Lindau tumor suppressor protein (Vhl), hypoxia-inducible factor (HIF)-1α, HIF-2α, and aryl hydrocarbon nuclear translocator (ARNT).
resultsWe observed biphasic regulation of Fpn during iron deficiency. Fpn was rapidly induced under conditions of low iron, which required the transcription factor HIF-2α. Targeted disruption of HIF-2α in the intestine inhibited Fpn induction in mice with low iron, through loss of transcriptional activation. Analysis of the Fpn promoter and in vivo chromatin immunoprecipitation assays demonstrated that HIF-2α directly binds to the Fpn promoter and induces its expression, indicating a mechanism of transcriptional regulation of Fpn following changes in systemic levels of iron. During chronic iron deficiency, FPN protein levels also increased, via increased stability through a HIF-2α-independent pathway.
conclusionsIn mice, expression of the gene that encodes Fpn and its protein levels are regulated by distinct pathways to provide a rapid and sustained response to acute and chronic iron deficiency. Therapies that target FPN might be developed for patients with iron-related 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.