Suppression of hepcidin during anemia requires erythropoietic activity
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Hepcidin, the principal iron regulatory hormone, regulates the absorption of iron from the diet and the mobilization of iron from stores. Previous studies indicated that hepcidin is suppressed during anemia, a response that would appropriately increase the absorption of iron and its release from stores. Indeed, in the mouse model, hepcidin-1 was suppressed after phlebotomy or erythropoietin administration but the suppression was reversed by inhibitors of erythropoiesis. The suppression of hepcidin necessary to match iron supply to erythropoietic demand thus requires increased erythropoiesis and is not directly mediated by anemia, tissue hypoxia, or erythropoietin.
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Anaemia and anoxia suppress hepcidin production, so while superoxide production is enhanced by anoxia, more iron is absorbed from the intestine and effluxed into the circulation.
“Strikingly, anaemia and anoxia both suppress hepcidin production [245,339,340] (Fig 3), such that just while superoxide production is being enhanced by the anoxia there is more iron being absorbed from the intestine and effluxed into the circulation.”
All animals received a low-iron diet for 5-7 days before and during experiments to bring baseline hepcidin to normal without causing iron deficiency.
“To correct this, all animals were conditioned on a low-iron diet (2-4 ppm iron; Teklad diet TD.80396, Envigo) for 5-7 days prior to, and throughout the duration of, all experiments.”
From Hepcidin-mediated iron sequestration protects against bacterial dissemination during pneumonia (2017) · cites this paper as [53]
HIF activation in hepatocytes suppresses hepcidin indirectly through EPO-mediated stimulation of erythropoiesis.
“Our data established that HIF activation in hepatocytes suppresses hepcidin indirectly through EPO-mediated stimulation of erythropoiesis”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [196]
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- Authors
- Pak, M., Lopez, M. A., Gabayan, V., Ganz, T., & Rivera, S.
- Affiliations
- University of California, Los Angeles (US)
- ORCID
- Ganz, Tomas
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-12-01
- Volume
- 108
- Issue
- 12
- Pages
- 3730-3735
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC1895477
- OpenAlex
- W1973313690
- Cited by
- 472
- References
- 40
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 10 · 2023: 16 · 2022: 10 · 2021: 22 · 2020: 18 · 2019: 16 · 2018: 21 · 2017: 38 · 2016: 15 · 2015: 27 · 2014: 37 · 2013: 37 · 2012: 35
- FWCI
- 16.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (K08 DK)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK065029, K08 DK 07284-01)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- hepcidin, anemia, erythropoiesis, erythropoietin, iron regulation, iron absorption, iron mobilization, phlebotomy, hypoxia
- MeSH terms
- Anemia, Animals, Hypoxia, Erythropoiesis, Erythropoietin, Female, Iron, Male, Iron, Dietary, Antimicrobial Cationic Peptides, Mice, Hepcidins
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