Cell-specific regulation of Ferroportin transcription following experimentally-induced acute anemia in mice
Open accessAbstract
Ferroportin (FPN), the sole characterized iron exporter, is mainly controlled by the peptide hormone hepcidin in response to iron, erythroid factors, hypoxia, and inflammation. In addition, intracellular iron level controls FPN translation by modulating the binding of Iron Responsive Proteins at the 5'UTR of FPN mRNA. Recently, hypoxia inducible factor (HIF)2α has been shown to regulate FPN expression in intestinal cells. Here we show that, during experimentally-induced acute anemia in mice, FPN is regulated at transcriptional level in a cell-specific manner. FPN mRNA level increases in duodenum and spleen macrophages, whereas it does not change in liver and is strongly down-regulated in erythroid precursors. These results were confirmed in Caco2, Raw264.7 and K562 cells treated with a hypoxic stimulus. Moreover, we found a differential expression of HIF1α and HIF2α in cells and tissues that might account for the specificity of FPN regulation. Thus, hypoxia, by directly controlling hepcidin and its target FPN, orchestrates a complex regulatory network aimed at ensuring rapid iron recovery from the periphery and efficient iron utilization in the erythroid compartment.
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HIF-HRE interaction in response to hypoxia stimulates iron release from macrophages by inducing Hmox1 and Fpn1 as well as ceruloplasmin.
“HIF-HRE interaction in response to hypoxia thus stimulates iron release from macrophages by inducing Hmox1 and Fpn1 as well as one of its associated ferroxidases, ceruloplasmin [37, 63, 200].”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [37]
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References 35 · Cited by 24
- Authors
- Chiabrando, D., Fiorito, V., Marro, S., Silengo, L., Altruda, F., & Tolosano, E.
- Affiliations
- University of Turin (IT)
- Institute for Stem Cell Biology and Regenerative Medicine (US)
- Corresponding author
- Tolosano, Emanuela
- Venue
- Blood Cells, Molecules, and Diseases
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 50
- Issue
- 1
- Pages
- 25-30
- ISSN
- 1079-9796 (ISSN-L)
- OpenAlex
- W1990953022
- Cited by
- 24
- References
- 35
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 1
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Blood Cells Molecules and Diseases (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- ferroportin, acute anemia, hypoxia, HIF-1α, HIF-2α, hepcidin, iron export, erythroid precursors, duodenal enterocytes, splenic macrophages, iron-responsive element, iron homeostasis, cell type-specific gene regulation
- MeSH terms
- Ferroportin, Endothelial PAS Domain-Containing Protein 1, Acute Disease, Anemia, Animals, Duodenum, Gene Expression Regulation, Humans, Iron, Liver, Macrophages, Male, Organ Specificity, RNA, Messenger, Spleen, Transcription, Genetic, Cell Hypoxia, Antimicrobial Cationic Peptides, Cation Transport Proteins, Cell Line, Tumor, Mice, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit, Hepcidins
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