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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gardenghi, S; Ramos, P; Marongiu, MF; Melchiori, L; Breda, L; Guy, E; Muirhead, K; Rao, N; Roy, CN; Andrews, NC; Nemeth, E; Follenzi, A; An, X; Mohandas, N; Ginzburg, Y; Rachmilewitz, EA; Giardina, PJ; Grady, RW; Rivella, S

Published Date

  • December 2010

Published In

Volume / Issue

  • 120 / 12

Start / End Page

  • 4466 - 4477

PubMed ID

  • 21099112

Pubmed Central ID

  • 21099112

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI41717

Language

  • eng