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Cited by 196Iron Metabolism and DisordersErythropoietin and Anemia TreatmentFerroptosis and cancer prognosis

Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia

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Rivera, Seth, Liu, Lide, Nemeth, Elizabeta, Gabayan, Victoria, Sorensen, Ole E., Ganz, Tomas·2005·Blood
DOI 10.1182/blood-2004-08-3375
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Abstract

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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  • Hepcidin peptide injected into mice is cleared from blood circulation within minutes, but its plasma iron lowering effect lasts for 24-48 h, supporting the importance of the endocytic mechanism for ferroportin physiology.

    “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]

    The Acute effects of hepcidin section (page unavailable) reports that injected hepcidin lowered serum iron in mice four hours later. It does not report clearance from circulation within minutes or show that the effect of a single injection lasts 24–48 hours. The passages also do not link this result to ferroportin endocytosis. (LLM, conf=0.89)

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  • Proinflammatory cytokines induced by inflammation can stimulate anemia of inflammation by limiting serum iron and increasing cellular iron stores through modulation of iron regulatory proteins including hepcidin, FPN, ferritin, and DMT1.

    “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]

  • Hepcidin binding to ferroportin leads to ubiquitinization, followed by internalization and degradation of FPN, resulting in iron trapped inside macrophages and hepatocytes and increased iron stores reflected in high serum ferritin.

    “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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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.
ORCID
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
DOI
10.1182/blood-2004-08-3375
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
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
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › 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

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