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

被引：28

作者：

Lenoir, Anne ^{[2
]}

Deschemin, Jean-Christophe ^{[2
]}

Kautz, Leon ^{[3
]}

Ramsay, Andrew J. ^{[4
]}

Roth, Marie-Paule ^{[3
]}

Lopez-Otin, Carlos ^{[4
]}

Vaulont, Sophie ^{[1
,2
]}

Nicolas, Gael ^{[1
,2
]}

机构：

[1] Univ Paris 05, Fac Med Cochin Port Royal, Dept Endocrinol Metab & Canc, Inst Cochin, F-75014 Paris, France

[2] INSERM, Paris, France

[3] Fac Med Toulouse, INSERM, F-31073 Toulouse, France

[4] Univ Oviedo, Dept Bioquim & Biol Mol, Inst Univ Oncol, Oviedo, Spain

来源：

BLOOD | 2011年 / 117卷 / 02期

关键词：

HEPCIDIN EXPRESSION; TMPRSS6; HOMEOSTASIS; HEMOJUVELIN; REGULATOR; METABOLISM; OVERLOAD; MICE;

D O I：

10.1182/blood-2010-07-295147

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (Blood. 2011;117(2):647-650)

引用

页码：647 / 650

页数：4

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