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Blood. 2011 Jan 13;117(2):647-50. doi: 10.1182/blood-2010-07-295147. Epub 2010 Oct 12.

Iron-deficiency anemia from matriptase-2 inactivation is dependent on the presence of functional Bmp6.

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1
Institut Cochin, Université Paris Descartes, Paris, France.

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.

PMID:
20940420
PMCID:
PMC3302207
DOI:
10.1182/blood-2010-07-295147
[Indexed for MEDLINE]
Free PMC Article
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