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

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.

• Authors: Anne Lenoir, Jean-Christophe Deschemin, Léon Kautz, Andrew J Ramsay, Marie-Paule Roth, Carlos Lopez-Otin, Sophie Vaulont, Gaël Nicolas
• Journal: Blood (Blood) Vol. 117 Issue 2 Pg. 647-50 (Jan 13 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 20940420 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimicrobial Cationic Peptides
• Bmp6 protein, mouse
• Bone Morphogenetic Protein 6
• Hamp protein, mouse
• Hepcidins
• Iron, Dietary
• Membrane Proteins
• Iron
• Serine Endopeptidases
• matriptase 2

Topics

• Anemia, Iron-Deficiency (metabolism)
• Animals
• Antimicrobial Cationic Peptides (metabolism)
• Bone Morphogenetic Protein 6 (metabolism)
• Female
• Hepcidins
• Iron (metabolism)
• Iron, Dietary (metabolism)
• Liver (metabolism)
• Membrane Proteins (metabolism)
• Mice
• Mice, Knockout
• Serine Endopeptidases (metabolism)
• Signal Transduction (physiology)