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dc.contributor.author Gardenghi, S
dc.contributor.author Ramos, P
dc.contributor.author Marongiu, MF
dc.contributor.author Melchiori, L
dc.contributor.author Breda, L
dc.contributor.author Guy, E
dc.contributor.author Muirhead, K
dc.contributor.author Rao, N
dc.contributor.author Roy, CN
dc.contributor.author Andrews, NC
dc.contributor.author Nemeth, E
dc.contributor.author Follenzi, A
dc.contributor.author An, X
dc.contributor.author Mohandas, N
dc.contributor.author Ginzburg, Y
dc.contributor.author Rachmilewitz, EA
dc.contributor.author Giardina, PJ
dc.contributor.author Grady, RW
dc.contributor.author Rivella, S
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:27:56Z
dc.date.issued 2010-12
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/21099112
dc.identifier 41717
dc.identifier.citation J Clin Invest, 2010, 120 (12), pp. 4466 - 4477
dc.identifier.uri http://hdl.handle.net/10161/4327
dc.description.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.
dc.format.extent 4466 - 4477
dc.language eng
dc.language.iso en_US en_US
dc.relation.ispartof J Clin Invest
dc.relation.isversionof 10.1172/JCI41717
dc.subject Animals
dc.subject Antimicrobial Cationic Peptides
dc.subject Base Sequence
dc.subject DNA Primers
dc.subject Disease Models, Animal
dc.subject Erythropoiesis
dc.subject Gene Expression
dc.subject Hepcidins
dc.subject Humans
dc.subject Iron
dc.subject Iron Overload
dc.subject Iron, Dietary
dc.subject Mice
dc.subject Mice, Inbred C57BL
dc.subject Mice, Mutant Strains
dc.subject Mice, Transgenic
dc.subject Recombinant Proteins
dc.subject beta-Thalassemia
dc.title Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-12-0 en_US
duke.description.endpage 4477 en_US
duke.description.issue 12 en_US
duke.description.startpage 4466 en_US
duke.description.volume 120 en_US
dc.relation.journal Journal of Clinical Investigation en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/21099112
pubs.issue 12
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Pharmacology & Cancer Biology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pediatrics
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.publication-status Published
pubs.volume 120
dc.identifier.eissn 1558-8238

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