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Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia
Open accessAbstract
The iron-regulatory hormone hepcidin has been proposed as the mediator of anemia of inflammation (AI). We examined the acute and chronic effects of hepcidin in the mouse. Injections of human hepcidin (50 μg/mouse), but not of its diluent, induced hypoferremia within 4 hours. To examine the chronic effects of hepcidin, we implanted either tumor xenografts engineered to overexpress human hepcidin or control tumor xenografts into nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice. Despite abundant dietary iron, mice with hepcidin-producing tumors developed more severe anemia, lower serum iron, and increased hepatic iron compared with mice with control tumors. Hepcidin contributes to AI by shunting iron away from erythropoiesis and sequestering it in the liver, predominantly in hepatocytes. (Blood. 2005;105:1797-1802)
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“Although hepcidin peptide injected into mice is cleared from blood circulation within minutes, its plasma iron lowering effect lasts for 24–48 h, supporting the importance of the endocytic mechanism for ferroportin physiology [18].”
From Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis (2021) · cites this paper as [18]
Experimental — accuracy not yet measuredIn the citing paper
“Proinflammatory cytokines induced by inflammation can stimulate anemia of inflammation by limiting serum iron and increasing cellular iron stores by modulating the expression and activity of various iron regulatory proteins including hepcidin, FPN, ferritin, and the iron importer divalent metal transporter 1 (DMT1) [25–30].”
From The utility of iron chelators in the management of inflammatory disorders (2015) · cites this paper as [29]
In the citing paper
“Hepcidin binding to ferroportin leads to ubiquitinization, followed by internalization and degradation of FPN [98]. The end result is that iron cannot be released into the plasma and remains trapped inside the macrophages and hepatocytes, resulting in an increase in iron stores reflected in high levels of serum ferritin [29].”
From The utility of iron chelators in the management of inflammatory disorders (2015) · cites this paper as [29]
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Metadata
- Authors
- Rivera, S., Liu, L., Nemeth, E., Gabayan, V., Sorensen, O. E., & Ganz, T.
- Affiliations
- University of California, Los Angeles (US)
- From the Departments of Medicine and Pathology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-02-15
- Volume
- 105
- Issue
- 4
- Pages
- 1797-1802
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2104991132
- Cited by
- 196
- References
- 25
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 3 · 2022: 3 · 2021: 8 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 4 · 2016: 7 · 2015: 6 · 2014: 9 · 2013: 11 · 2012: 11
- FWCI
- 9.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK065029, R01DK065029)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Keywords
- hepcidin, anemia of chronic disease, iron sequestration, hypoferremia, hepatic iron deposition, erythropoiesis, iron regulation, tumor xenografts, NOD/SCID mice, hepatocytes
- MeSH terms
- Animals, Cell Line, Drug Administration Schedule, Humans, Iron, Liver Neoplasms, Experimental, Lung Neoplasms, Mice, Inbred C57BL, Neoplasm Transplantation, Transplantation, Heterologous, Tumor Virus Infections, Mice, SCID, Mice, Inbred NOD, Anemia, Iron-Deficiency, Caco-2 Cells, Iron, Dietary, Antimicrobial Cationic Peptides, Cell Line, Tumor, Mice, Hepcidins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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