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Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice.

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Date
2010-12
Authors
Gardenghi, Sara
Ramos, Pedro
Marongiu, Maria Franca
Melchiori, Luca
Breda, Laura
Guy, Ella
Muirhead, Kristen
Rao, Niva
Roy, Cindy N
Andrews, Nancy C
Nemeth, Elizabeta
Follenzi, Antonia
An, Xiuli
Mohandas, Narla
Ginzburg, Yelena
Rachmilewitz, Eliezer A
Giardina, Patricia J
Grady, Robert W
Rivella, Stefano
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(19 total)
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Abstract
Excessive iron absorption is one of the main features of β-thalassemia and can lead to severe morbidity and mortality. Serial analyses of β-thalassemic mice indicate that while hemoglobin levels decrease over time, the concentration of iron in the liver, spleen, and kidneys markedly increases. Iron overload is associated with low levels of hepcidin, a peptide that regulates iron metabolism by triggering degradation of ferroportin, an iron-transport protein localized on absorptive enterocytes as well as hepatocytes and macrophages. Patients with β-thalassemia also have low hepcidin levels. These observations led us to hypothesize that more iron is absorbed in β-thalassemia than is required for erythropoiesis and that increasing the concentration of hepcidin in the body of such patients might be therapeutic, limiting iron overload. Here we demonstrate that a moderate increase in expression of hepcidin in β-thalassemic mice limits iron overload, decreases formation of insoluble membrane-bound globins and reactive oxygen species, and improves anemia. Mice with increased hepcidin expression also demonstrated an increase in the lifespan of their red cells, reversal of ineffective erythropoiesis and splenomegaly, and an increase in total hemoglobin levels. These data led us to suggest that therapeutics that could increase hepcidin levels or act as hepcidin agonists might help treat the abnormal iron absorption in individuals with β-thalassemia and related disorders.
Type
Journal article
Subject
Animals
Antimicrobial Cationic Peptides
Base Sequence
DNA Primers
Disease Models, Animal
Erythropoiesis
Gene Expression
Hepcidins
Humans
Iron
Iron Overload
Iron, Dietary
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Mice, Transgenic
Recombinant Proteins
beta-Thalassemia
Permalink
https://hdl.handle.net/10161/4327
Published Version (Please cite this version)
10.1172/JCI41717
Publication Info
Gardenghi, Sara; Ramos, Pedro; Marongiu, Maria Franca; Melchiori, Luca; Breda, Laura; Guy, Ella; ... Rivella, Stefano (2010). Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice. J Clin Invest, 120(12). pp. 4466-4477. 10.1172/JCI41717. Retrieved from https://hdl.handle.net/10161/4327.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Andrews

Nancy Catherine Andrews

Adjunct Professor in the Department of Pharmacology and Cancer Biology
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