ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2015
Erythropoietin's inhibiting impact on hepcidin expression occurs indirectly.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 60 citations in OpenAlex.
- Changes in the Serum Hepcidin-to-ferritin Ratio with Erythroferrone after Hepatitis C Virus Eradication Using Direct-acting Antiviral Agents.Internal medicine (Tokyo, Japan) · 2019Trial
- Trial
- Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019Trial
- Erythropoietin stimulates fibroblast growth factor 23 (FGF23) in mice and men.Pflugers Archiv : European journal of physiology · 2018Trial
- Effect of 2-h hypoxic exposure on resting hepcidin levels in young adults.Physiological reports · 2025Article
- Molecular Mechanisms of Iron Metabolism and Overload.Biomedicines · 2025Review
- Influence of TMPRSS6 genotype on iron status parameters in stable COPD patients.Journal of medical biochemistry · 2025Article
- Outline of Iron Metabolism, with Emphasis on Erythroid Cells.Mediterranean journal of hematology and infectious diseases · 2025Review
- Multicomponent comprehensive confirms that erythroferrone is a molecular biomarker of pan-cancer.Heliyon · 2024Article
- Article
- Drugs activating hypoxia-inducible factors correct erythropoiesis and hepcidin levels via renal EPO induction in mice.Blood advances · 2023Article
- HIF2α, Hepcidin and their crosstalk as tumour-promoting signalling.British journal of cancer · 2023Review
- Placental Erythroferrone and Erythropoietin mRNA Expression is not Associated with Maternal or Neonatal Iron Status in Adolescents Carrying Singletons and Adult Women Carrying Multiples.The Journal of nutrition · 2023Article
- How can sodium-glucose cotransporter 2 inhibitors stimulate erythrocytosis in patients who are iron-deficient? Implications for understanding iron homeostasis in heart failure.European journal of heart failure · 2022Review
- Iron Mining for Erythropoiesis.International journal of molecular sciences · 2022Review
- Prolyl hydroxylase inhibitor desidustat improves anemia in erythropoietin hyporesponsive state.Current research in pharmacology and drug discovery · 2022Article
- Essential role of systemic iron mobilization and redistribution for adaptive thermogenesis through HIF2-α/hepcidin axis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Erythroferrone structure, function, and physiology: Iron homeostasis and beyond.Journal of cellular physiology · 2021Review
- Iron status and erythropoiesis response to darbepoetin alfa in dogs with chronic kidney disease.The Journal of veterinary medical science · 2021Article
- Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 4 countries.
Funding
Abstract
Under conditions of accelerated erythropoiesis, elevated erythropoietin (Epo) levels are associated with inhibition of hepcidin synthesis, a response that ultimately increases iron availability to meet the enhanced iron needs of erythropoietic cells. In the search for erythroid regulators of hepcidin, many candidates have been proposed, including Epo itself. We aimed to test whether direct interaction between Epo and the liver is required to regulate hepcidin. We found that prolonged administration of high doses of Epo in mice leads to great inhibition of liver hepcidin mRNA levels, and concomitant induction of the hepcidin inhibitor erythroferrone (ERFE). Epo treatment also resulted in liver iron mobilization, mediated by increased ferroportin activity and accompanied by reduced ferritin levels and increased TfR1 expression. The same inhibitory effect was observed in mice that do not express the homodimeric Epo receptor (EpoR) in liver cells because EpoR expression is restricted to erythroid cells. Similarly, liver signaling pathways involved in hepcidin regulation were not influenced by the presence or absence of hepatic EpoR. Moreover, Epo analogs, possibly interacting with the postulated heterodimeric β common EpoR, did not affect hepcidin expression. These findings were supported by the lack of inhibition on hepcidin found in hepatoma cells exposed to various concentrations of Epo for different periods of times. Our results demonstrate that hepcidin suppression does not require the direct binding of Epo to its liver receptors and rather suggest that the role of Epo is to stimulate the synthesis of the erythroid regulator ERFE in erythroblasts, which ultimately downregulates hepcidin.
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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.