Journal article
Erythroferrone inhibits the induction of hepcidin by BMP6
J Arezes, N Foy, K McHugh, A Sawant, D Quinkert, V Terraube, A Brinth, M Tam, ER LaVallie, S Taylor, AE Armitage, SR Pasricha, O Cunningham, M Lambert, SJ Draper, R Jasuja, H Drakesmith
Blood | AMER SOC HEMATOLOGY | Published : 2018
Abstract
Decreased hepcidin mobilizes iron, which facilitates erythropoiesis, but excess iron is pathogenic in b-thalassemia. Erythropoietin (EPO) enhances erythroferrone (ERFE) synthesis by erythroblasts, and ERFE suppresses hepatic hepcidin production through an unknown mechanism. The BMP/SMAD pathway in the liver is critical for hepcidin control, andwe show that EPO suppressed hepcidin and other BMP target genes in vivo in a partially ERFE-dependent manner. Furthermore, recombinant ERFE suppressed the hepatic BMP/SMAD pathway independently of changes in serum and liver iron. In vitro, ERFE decreased SMAD1, SMAD5, and SMAD8 phosphorylation and inhibited expression of BMP target genes. ERFE specific..
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Awarded by Pfizer
Funding Acknowledgements
This work was funded by a Pfizer-sponsored Rare Disease Consortium Award, and the Medical Research Council United Kingdom (MRC Human Immunology Unit core funding) (H.D.). S.J.D. is a Jenner Investigator, a Lister Institute Research Prize Fellow, and a Wellcome Trust Senior Fellow (106917/Z/15/Z).