ArticleNature metabolism2019
Nrf2 controls iron homeostasis in haemochromatosis and thalassaemia via Bmp6 and hepcidin.
Article in Nature metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
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Who cites it
70 citing papers in PubMed, 135 citations in OpenAlex.
- Hepcidin as a Molecular Hub of Iron Homeostasis: From BMP-SMAD Signaling to Therapeutic Modulation.Biomolecules · 2026Review
- Article
- Targeting ferroptosis as a therapeutic strategy for hepatotoxicity.Toxicology reports · 2025Review
- Ferroptosis as a key player in the pathogenesis and intervention therapy in liver injury: focusing on drug-induced hepatotoxicity.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Molecular Mechanisms of Iron Metabolism and Overload.Biomedicines · 2025Review
- Iron metabolism and ferroptosis in human health and disease.BMC biology · 2025Review
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- Redox imbalance drives magnetic property and function changes in mice.Redox biology · 2025Article
- Evaluated NSUN3 in reticulocytes from HbH-CS disease that reflects cellular stress in erythroblasts.Annals of hematology · 2025Article
- HFE-Related Hemochromatosis May Be a Primary Kupffer Cell Disease.Biomedicines · 2025Review
- The GPR30-Mediated BMP-6/HEP/FPN Signaling Pathway Inhibits Ferroptosis in Bone Marrow Mesenchymal Stem Cells to Alleviate Osteoporosis.International journal of molecular sciences · 2025Article
- Article
- Control of Systemic Iron Homeostasis: Insights Gained from Studying Mouse Models.Advances in experimental medicine and biology · 2025Review
- Role of NRF2 in Pathogenesis of Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Sevuparin strongly reduces hepcidin expression in cells, mice, and healthy human volunteers.HemaSphere · 2024Article
- SGK1 suppresses ferroptosis in ovarian cancer via NRF2-dependent and -independent pathways.Oncogene · 2024Article
- Serum Iron Overload Triggers the SMAD Pathway and Induces Hepcidin Expression in Hepatocytes through SMURF1.Journal of clinical and translational hepatology · 2024Article
- Hemojuvelin-mediated hepcidin induction requires both bone morphogenetic protein type I receptors ALK2 and ALK3.Blood advances · 2024Article
- Article
- Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression.Biomolecules · 2024Review
10 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
24 authors at 9 institutions in 5 countries.
Funding
Abstract
Iron is critical for life but toxic in excess because of iron-catalysed formation of pro-oxidants that cause tissue damage in a range of disorders. The Nrf2 transcription factor orchestrates cell-intrinsic protective antioxidant responses, and the peptide hormone hepcidin maintains systemic iron homeostasis, but is pathophysiologically decreased in haemochromatosis and beta-thalassaemia. Here, we show that Nrf2 is activated by iron-induced, mitochondria-derived pro-oxidants and drives Bmp6 expression in liver sinusoid endothelial cells, which in turn increases hepcidin synthesis by neighbouring hepatocytes. In Nrf2 knockout mice, the Bmp6-hepcidin response to oral and parenteral iron is impaired and iron accumulation and hepatic damage are increased. Pharmacological activation of Nrf2 stimulates the Bmp6-hepcidin axis, improving iron homeostasis in haemochromatosis and counteracting the inhibition of Bmp6 by erythroferrone in beta-thalassaemia. We propose that Nrf2 links cellular sensing of excess toxic iron to control of systemic iron homeostasis and antioxidant responses, and may be a therapeutic target for iron-associated disorders.
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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.