Publication: High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin
Issued Date
2007-09-01
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ISSN
1546170X
10788956
10788956
DOI
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2-s2.0-34948904750
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Mahidol University
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SCOPUS
Bibliographic Citation
Nature Medicine. Vol.13, No.9 (2007), 1096-1101
Suggested Citation
Toshihiko Tanno, Natarajan V. Bhanu, Patricia A. Oneal, Sung Ho Goh, Pamela Staker, Y. Terry Lee, John W. Moroney, Christopher H. Reed, Naomi L.C. Luban, Rui Hong Wang, Thomas E. Eling, Richard Childs, Tomas Ganz, Susan F. Leitman, Suthat Fucharoen, Jeffery L. Miller High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nature Medicine. Vol.13, No.9 (2007), 1096-1101. doi:10.1038/nm1629 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/24137
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Title
High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin
Other Contributor(s)
National Institute of Diabetes and Digestive and Kidney Diseases
Walter Reed National Military Medical Center
Childrens National Health System
National Institute of Environmental Health Sciences
National Heart, Lung, and Blood Institute
David Geffen School of Medicine at UCLA
National Institutes of Health, Bethesda
The Institute of Science and Technology for Research and Development, Mahidol University
Walter Reed National Military Medical Center
Childrens National Health System
National Institute of Environmental Health Sciences
National Heart, Lung, and Blood Institute
David Geffen School of Medicine at UCLA
National Institutes of Health, Bethesda
The Institute of Science and Technology for Research and Development, Mahidol University
Abstract
In thalassemia, deficient globin-chain production during erythropoiesis results in anemia. Thalassemia may be further complicated by iron overload (frequently exacerbated by blood transfusion), which induces numerous endocrine diseases, hepatic cirrhosis, cardiac failure and even death. Accumulation of iron in the absence of blood transfusions may result from inappropriate suppression of the iron-regulating peptide hepcidin by an erythropoietic mechanism. To test this hypothesis, we examined erythroblast transcriptome profiles from 15 healthy, nonthalassemic donors. Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-β superfamily, showed increased expression and secretion during erythroblast maturation. Healthy volunteers had mean GDF15 serum concentrations of 450 ± 50 pg/ml. In comparison, individuals with β-thalassemia syndromes had elevated GDF15 serum levels (mean 66,000 ± 9,600 pg/ml; range 4,800-248,000 pg/ml; P < 0.05) that were positively correlated with the levels of soluble transferrin receptor, erythropoietin and ferritin. Serum from thalassemia patients suppressed hepcidin mRNA expression in primary human hepatocytes, and depletion of GDF15 reversed hepcidin suppression. These results suggest that GDF15 overexpression arising from an expanded erythroid compartment contributes to iron overload in thalassemia syndromes by inhibiting hepcidin expression. © 2007 Nature Publishing Group.
