Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice.
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 articleSubject
AnimalsAntimicrobial 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
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https://hdl.handle.net/10161/4327Published Version (Please cite this version)
10.1172/JCI41717Publication 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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Nancy Catherine Andrews
Adjunct Professor in the Department of Pharmacology and Cancer Biology

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