Iron-deficiency anemia from matriptase-2 inactivation is dependent on the presence of functional Bmp6.: Matriptase-2 and Bmp6 deficiency in mice

Anne Lenoir 1 Jean-Christophe Deschemin 1 Léon Kautz 2 Andrew Ramsay 3 Marie-Paule Roth 2 Carlos Lopez-Otin 3 Sophie Vaulont 1 Gaël Nicolas 1, *
* Auteur correspondant
1 UM3 (UMR 8104 / U1016) - Institut Cochin
2 Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150)
3 Departamento de Bioquímica y Biología Molecular
Abstract : Hepcidin is the master regulator of iron homeostasis. In the liver, iron-dependent hepcidin activation is regulated through Bmp6 and its membrane receptor hemojuvelin (Hjv), whereas, in response to iron deficiency, hepcidin repression seems to be controlled by a pathway involving the serine protease matriptase-2 (encoded by Tmprss6). To determine the relationship between Bmp6 and matriptase-2 pathways, Tmprss6(-/-) mice (characterized by increased hepcidin levels and anemia) and Bmp6(-/-) mice (exhibiting severe iron overload because of hepcidin deficiency) were intercrossed. We showed that loss of Bmp6 decreased hepcidin levels; increased hepatic iron; and, importantly, corrected hematologic abnormalities in Tmprss6(-/-) mice. This finding suggests that elevated hepcidin levels in patients with familial iron-refractory, iron-deficiency anemia are the result of excess signaling through the Bmp6/Hjv pathway.
keyword : hepcidin hemojuvelin bmp6 matriptase2 tmprss6
Type de document :
Article dans une revue
Blood, American Society of Hematology, 2011, 117 (2), pp.647-50. 〈10.1182/blood-2010-07-295147〉
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Contributeur : Gaël Nicolas <>
Soumis le : mercredi 5 janvier 2011 - 13:36:28
Dernière modification le : mardi 11 septembre 2018 - 15:18:46
Document(s) archivé(s) le : mercredi 6 avril 2011 - 02:51:48

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Anne Lenoir, Jean-Christophe Deschemin, Léon Kautz, Andrew Ramsay, Marie-Paule Roth, et al.. Iron-deficiency anemia from matriptase-2 inactivation is dependent on the presence of functional Bmp6.: Matriptase-2 and Bmp6 deficiency in mice. Blood, American Society of Hematology, 2011, 117 (2), pp.647-50. 〈10.1182/blood-2010-07-295147〉. 〈inserm-00552073〉

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