Hepcidin regulates ferroportin expression and intracellular iron homeostasis of erythroblasts
Open accessAbstract
The iron-regulatory hormone, hepcidin, regulates systemic iron homeostasis by interacting with the iron export protein ferroportin (FPN1) to adjust iron absorption in enterocytes, iron recycling through reticuloendothelial macrophages, and iron release from storage in hepatocytes. We previously demonstrated that FPN1 was highly expressed in erythroblasts, a cell type that consumes most of the serum iron for use in hemoglobin synthesis. Herein, we have demonstrated that FPN1 localizes to the plasma membrane of erythroblasts, and hepcidin treatment leads to decreased expression of FPN1 and a subsequent increase in intracellular iron concentrations in both erythroblast cell lines and primary erythroblasts. Moreover, injection of exogenous hepcidin decreased FPN1 expression in BM erythroblasts in vivo, whereas iron depletion and associated hepcidin reduction led to increased FPN1 expression in erythroblasts. Taken together, hepcidin decreased FPN1 expression and increased intracellular iron availability of erythroblasts. We hypothesize that FPN1 expression in erythroblasts allows fine-tuning of systemic iron utilization to ensure that erythropoiesis is partially suppressed when nonerythropoietic tissues risk developing iron deficiency. Our results may explain why iron deficiency anemia is the most pronounced early manifestation of mammalian iron deficiency.
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After hepcidin injection, serum iron levels were higher in Rnf217Lysm/Lysm mice than in hepcidin-treated Rnf217flox/flox mice.
“We found that 2 injections of hepcidin19 led to higher levels of both splenic FPN (Figure 6G-H; supplemental Figure 11A) and serum iron levels (Figure 6I) in the Rnf217Lysm/Lysm mice compared with hepcidin-treated Rnf217flox/flox mice”
From RNF217 regulates iron homeostasis through its E3 ubiquitin ligase activity by modulating ferroportin degradation (2021) · cites this paper as [19]
After hepcidin injection, splenic FPN levels were higher in Rnf217Lysm/Lysm mice than in hepcidin-treated Rnf217flox/flox mice.
“We found that 2 injections of hepcidin19 led to higher levels of both splenic FPN (Figure 6G-H; supplemental Figure 11A) and serum iron levels (Figure 6I) in the Rnf217Lysm/Lysm mice compared with hepcidin-treated Rnf217flox/flox mice”
From RNF217 regulates iron homeostasis through its E3 ubiquitin ligase activity by modulating ferroportin degradation (2021) · cites this paper as [19]
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Self-citation
- Authors
- Zhang, D.-L., Senecal, T., Ghosh, M. C., Ollivierre-Wilson, H., Tu, T., & Rouault, T. A.
- Affiliations
- National Institutes of Health (US)
- Molecular Medicine Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-09-08
- Volume
- 118
- Issue
- 10
- Pages
- 2868-2877
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC3172802
- OpenAlex
- W2024502167
- Cited by
- 113
- References
- 36
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 13 · 2023: 8 · 2022: 5 · 2021: 7 · 2020: 4 · 2019: 7 · 2018: 11 · 2017: 6 · 2016: 7 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 6
- FWCI
- 5.47
- 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
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- hepcidin, ferroportin, ferroportin 1, erythroblasts, iron deficiency anemia, erythropoiesis, iron regulation, plasma membrane localization, bone marrow erythroblasts, iron deficiency
- MeSH terms
- Ferroportin, Animals, Cell Membrane, Erythroblasts, Fetus, Homeostasis, Iron, Liver, Mice, Inbred C57BL, RNA, Messenger, Blotting, Western, Iron, Dietary, Reverse Transcriptase Polymerase Chain Reaction, Antimicrobial Cationic Peptides, Electrophoretic Mobility Shift Assay, Cation Transport Proteins, Immunoprecipitation, Mice, Hepcidins
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