Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia
Open accessAbstract
Inherited anemias with ineffective erythropoiesis, such as β-thalassemia, manifest inappropriately low hepcidin production and consequent excessive absorption of dietary iron, leading to iron overload. Erythroferrone (ERFE) is an erythroid regulator of hepcidin synthesis and iron homeostasis. Erfe expression was highly increased in the marrow and spleen of HbbTh3/+ mice (Th3/+), a mouse model of thalassemia intermedia. Ablation of Erfe in Th3/+ mice restored normal levels of circulating hepcidin at 6 weeks of age, suggesting ERFE could be a factor suppressing hepcidin production in β-thalassemia. We examined the expression of Erfe and the consequences of its ablation in thalassemic mice from 3 to 12 weeks of age. The loss of ERFE in thalassemic mice led to full restoration of hepcidin mRNA expression at 3 and 6 weeks of age, and significant reduction in liver and spleen iron content at 6 and 12 weeks of age. Ablation of Erfe slightly ameliorated ineffective erythropoiesis, as indicated by reduced spleen index, red cell distribution width, and mean corpuscular volume, but did not improve the anemia. Thus, ERFE mediates hepcidin suppression and contributes to iron overload in a mouse model of β-thalassemia.
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ERFE contributes to iron loading in mice with β-thalassemia.
“However, ERFE contributes to iron loading in mice with β-thalassemia.74”
From Iron metabolism and iron disorders revisited in the hepcidin era (2020) · cites this paper as [74]
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- Authors
- Kautz, L., Jung, G., Du, X., Gabayan, V., Chapman, J., Nasoff, M., Nemeth, E., & Ganz, T.
- Affiliations
- Department of Medicine and
- Silarus Therapeutics, La Jolla, CA
- University of California, Los Angeles (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2015-10-22
- Volume
- 126
- Issue
- 17
- Pages
- 2031-2037
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC4616236
- OpenAlex
- W1844334486
- Cited by
- 306
- References
- 9
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 25 · 2023: 27 · 2022: 29 · 2021: 30 · 2020: 32 · 2019: 36 · 2018: 29 · 2017: 34 · 2016: 29 · 2015: 3
- FWCI
- 24.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Society of Hematology
- National Institutes of Health
- National Cancer Institute (P30CA016042)
- National Institute of Allergy and Infectious Diseases (P30AI028697)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK065029)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- erythroferrone, hepcidin, iron overload, beta-thalassemia, thalassemia intermedia, iron homeostasis, ineffective erythropoiesis, spleen iron, liver iron, anemia
- MeSH terms
- Animals, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Erythropoiesis, Female, Male, Mice, Inbred C57BL, Muscle Proteins, RNA, Messenger, Cytokines, beta-Thalassemia, Mice, Knockout, Iron Overload, Reverse Transcriptase Polymerase Chain Reaction, Mice, Real-Time Polymerase Chain Reaction, Hepcidins
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