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

Sara Gardenghi, Pedro Ramos, Maria Franca Marongiu, Luca Melchiori, Laura Breda, Ella Guy, Kristen Muirhead, Niva Rao, Cindy N. Roy, Nancy C. Andrews, Elizabeta Nemeth, Antonia Follenzi, Xiuli An, Narla Mohandas, Yelena Ginzburg, Eliezer A. Rachmilewitz, Patricia J. Giardina, Robert W. Grady, Stefano Rivella

Research output: Contribution to journalArticle


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.

Original languageEnglish (US)
Pages (from-to)4466-4477
Number of pages12
JournalJournal of Clinical Investigation
Issue number12
StatePublished - Dec 1 2010

ASJC Scopus subject areas

  • Medicine(all)

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    Gardenghi, S., Ramos, P., Marongiu, M. F., Melchiori, L., Breda, L., Guy, E., Muirhead, K., Rao, N., Roy, C. N., Andrews, N. C., Nemeth, E., Follenzi, A., An, X., Mohandas, N., Ginzburg, Y., Rachmilewitz, E. A., Giardina, P. J., Grady, R. W., & Rivella, S. (2010). Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice. Journal of Clinical Investigation, 120(12), 4466-4477. https://doi.org/10.1172/JCI41717