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Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2010 Dec; Vol. 120 (12), pp. 4466-77. Date of Electronic Publication: 2010 Nov 22. - Publication Year :
- 2010
-
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.
- Subjects :
- Animals
Antimicrobial Cationic Peptides genetics
Base Sequence
DNA Primers genetics
Disease Models, Animal
Erythropoiesis drug effects
Gene Expression
Hepcidins
Humans
Iron metabolism
Iron Overload blood
Iron Overload metabolism
Iron, Dietary administration & dosage
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Mice, Transgenic
Recombinant Proteins genetics
Recombinant Proteins therapeutic use
beta-Thalassemia blood
beta-Thalassemia metabolism
Antimicrobial Cationic Peptides therapeutic use
Iron Overload drug therapy
beta-Thalassemia drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 120
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 21099112
- Full Text :
- https://doi.org/10.1172/JCI41717