Toshihiko TannoNatarajan V. BhanuPatricia A. OnealSung Ho GohPamela StakerY. Terry LeeJohn W. MoroneyChristopher H. ReedNaomi L.C. LubanRui Hong WangThomas E. ElingRichard ChildsTomas GanzSusan F. LeitmanSuthat FucharoenJeffery L. MillerNational Institute of Diabetes and Digestive and Kidney DiseasesWalter Reed National Military Medical CenterChildrens National Health SystemNational Institute of Environmental Health SciencesNational Heart, Lung, and Blood InstituteDavid Geffen School of Medicine at UCLANational Institutes of Health, BethesdaThe Institute of Science and Technology for Research and Development, Mahidol University2018-08-242018-08-242007-09-01Nature Medicine. Vol.13, No.9 (2007), 1096-11011546170X107889562-s2.0-34948904750https://repository.li.mahidol.ac.th/handle/123456789/24137In 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/nm1629