For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
102
views
37
references
 Top references
cited by
183
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      229
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      IDENTIFICATION OF ERYTHROFERRONE AS AN ERYTHROID REGULATOR OF IRON METABOLISM

      research-article
      Author(s): , PhD 1 , , MS 1 , , MS 1 , , PhD 3 , 4 , , PhD 1 , , MD, PhD 1 , 2
      Publication date (Electronic):
      Journal: Nature genetics

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Recovery from blood loss requires a greatly enhanced supply of iron to support expanded erythropoiesis. After hemorrhage, suppression of the iron-regulatory hormone hepcidin allows increased iron absorption and mobilization from stores. We identified a new hormone, erythroferrone (ERFE), which mediates hepcidin suppression during stress erythropoiesis. ERFE is produced by erythroblasts in response to erythropoietin. ERFE-deficient mice fail to suppress hepcidin rapidly after hemorrhage and exhibit a delay in recovery from blood loss. ERFE expression is greatly increased in murine Hbb Th3/+ thalassemia intermedia where it contributes to the suppression of hepcidin and systemic iron overload characteristic of this disease.

          Related collections

          Most cited references37

          • Record: found
          • Abstract: found
          • Article: not found

          BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism.

          Billy Andriopoulos, Elena Corradini, Yin Xia … (2009)
          Juvenile hemochromatosis is an iron-overload disorder caused by mutations in the genes encoding the major iron regulatory hormone hepcidin (HAMP) and hemojuvelin (HFE2). We have previously shown that hemojuvelin is a co-receptor for bone morphogenetic proteins (BMPs) and that BMP signals regulate hepcidin expression and iron metabolism. However, the endogenous BMP regulator(s) of hepcidin in vivo is unknown. Here we show that compared with soluble hemojuvelin (HJV.Fc), the homologous DRAGON.Fc is a more potent inhibitor of BMP2 or BMP4 but a less potent inhibitor of BMP6 in vitro. In vivo, HJV.Fc or a neutralizing antibody to BMP6 inhibits hepcidin expression and increases serum iron, whereas DRAGON.Fc has no effect. Notably, Bmp6-null mice have a phenotype resembling hereditary hemochromatosis, with reduced hepcidin expression and tissue iron overload. Finally, we demonstrate a physical interaction between HJV.Fc and BMP6, and we show that BMP6 increases hepcidin expression and reduces serum iron in mice. These data support a key role for BMP6 as a ligand for hemojuvelin and an endogenous regulator of hepcidin expression and iron metabolism in vivo.
          Article 0 comments Cited 213 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs).

            Annelies S Zinkernagel, Victor Nizet, Reto A Schuepbach … (2007)
            Iron is essential for many biological processes, including oxygen delivery, and its supply is tightly regulated. Hepcidin, a small peptide synthesized in the liver, is a key regulator of iron absorption and homeostasis in mammals. Hepcidin production is increased by iron overload and decreased by anemia and hypoxia; but the molecular mechanisms that govern the hepcidin response to these stimuli are not known. Here we establish that the von Hippel-Lindau/hypoxia-inducible transcription factor (VHL/HIF) pathway is an essential link between iron homeostasis and hepcidin regulation in vivo. Through coordinate downregulation of hepcidin and upregulation of erythropoietin and ferroportin, the VHL-HIF pathway mobilizes iron to support erythrocyte production.
            Article 0 comments Cited 158 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Lack of the bone morphogenetic protein BMP6 induces massive iron overload.

              Delphine Meynard, Léon Kautz, Valérie Darnaud … (2009)
              Expression of hepcidin, a key regulator of intestinal iron absorption, can be induced in vitro by several bone morphogenetic proteins (BMPs), including BMP2, BMP4 and BMP9 (refs. 1,2). However, in contrast to BMP6, expression of other BMPs is not regulated at the mRNA level by iron in vivo, and their relevance to iron homeostasis is unclear. We show here that targeted disruption of Bmp6 in mice causes a rapid and massive accumulation of iron in the liver, the acinar cells of the exocrine pancreas, the heart and the renal convoluted tubules. Despite their severe iron overload, the livers of Bmp6-deficient mice have low levels of phosphorylated Smad1, Smad5 and Smad8, and these Smads are not significantly translocated to the nucleus. In addition, hepcidin synthesis is markedly reduced. This indicates that Bmp6 is critical for iron homeostasis and that it is functionally nonredundant with other members of the Bmp subfamily. Notably, Bmp6-deficient mice retain their capacity to induce hepcidin in response to inflammation. The iron burden in Bmp6 mutant mice is significantly greater than that in mice deficient in the gene associated with classical hemochromatosis (Hfe), suggesting that mutations in BMP6 might cause iron overload in humans with severe juvenile hemochromatosis for which the genetic basis has not yet been characterized.
              Article 0 comments Cited 147 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-journal-id): 9216904
                Journal ID (pubmed-jr-id): 2419
                Journal ID (nlm-ta): Nat Genet
                Journal ID (iso-abbrev): Nat. Genet.
                Title: Nature genetics
                ISSN (Print): 1061-4036
                ISSN (Electronic): 1546-1718
                Publication date Nihms-submitted: 31 May 2014
                Publication date (Electronic): 01 June 2014
                Publication date (Print): July 2014
                Publication date PMC-release: 01 January 2015
                Volume: 46
                Issue: 7
                Pages: 678-684
                Affiliations
                [1 ]Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
                [2 ]Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
                [3 ]Department of Pediatrics, Division of Hematology-Oncology, Weill Cornell Medical College, New York, USA
                [4 ]Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, USA
                Author notes
                Corresponding author: Tomas Ganz, UCLA, Department of Medicine, 10833 LeConte Ave, CHS 37-131, Los Angeles, CA 90095, Phone: 310-825-7499, Fax: 310-206-8766, tganz@ 123456mednet.ucla.edu
                Article
                Manuscript ID: NIHMS594179
                DOI: 10.1038/ng.2996
                PMC ID: 4104984
                PubMed ID: 24880340
                SO-VID: 4719882c-81bd-4f6b-8d14-264b8106a295
                History
                Categories
                Subject: Article

                ScienceOpen disciplines: Genetics
                Data availability:
                ScienceOpen disciplines: Genetics

                Comments

                Comment on this article