title: Matriptase-2 is essential for hepcidin repression during fetal life and postnatal development in mice to maintain iron homeostasis.
abstract: Iron is an essential element required for development and survival of all living organisms. In fetuses, maternofetal iron transfer across the placenta is essential for growth and development. In neonates, efficient intestinal iron absorption is required to scavenge as much iron as possible from the low-iron-content milk. During these periods, efficient iron mobilization is ensured by the downregulation of the iron regulatory hormone hepcidin by as-yet uncharacterized molecular mechanisms. Here we demonstrate that the recently described hepcidin repressor-the serine protease matriptase-2 (encoded by Tmprss6)-is responsible for this repression throughout development, with its deficiency leading to increased hepcidin levels triggering iron deficiency and anemia starting in utero. This result might have implications for a better understanding of iron homeostasis during early development in iron-refractory iron deficiency anemia patients, who present with microcytic anemia caused by hyperhepcidinemia, and of questions about the role of matriptase-2 in human neonates.
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratory of Excellence GR-Ex; and.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Willemetz
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratory of Excellence GR-Ex; and.
authors.forename: Anne
authors.initials: A
authors.lastname: Lenoir
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratory of Excellence GR-Ex; and.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Deschemin
authors.affiliation: Departamento de Bioquimica y Biologia Molecular, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopez-Otin
authors.affiliation: Departamento de Bioquimica y Biologia Molecular, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ramsay
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratory of Excellence GR-Ex; and.
authors.forename: Sophie
authors.initials: S
authors.lastname: Vaulont
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratory of Excellence GR-Ex; and.
authors.forename: Gaël
authors.identifier: http://orcid.org/0000-0002-1671-8274
authors.initials: G
authors.lastname: Nicolas
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000209:etiology; D000818:Animals; D055418:Bone Morphogenetic Protein 6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005333:Fetus / Q000378:metabolism; D058851:GPI-Linked Proteins; D000071020:Hemochromatosis Protein; D064451:Hepcidins / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D000090463:Iron Deficiencies; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011247:Pregnancy; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C525817:Bmp6 protein, mouse; D055418:Bone Morphogenetic Protein 6; D058851:GPI-Linked Proteins; C504414:HJV protein, mouse; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D008565:Membrane Proteins; D007501:Iron; D012697:Serine Endopeptidases; C467801:matriptase 2