{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:54:07Z","timestamp":1791298447314,"version":"4.1.0"},"reference-count":20,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,1,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u2212\/\u2212 mice (characterized by increased hepcidin levels and anemia) and Bmp6\u2212\/\u2212 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\u2212\/\u2212 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.<\/jats:p>","DOI":"10.1182\/blood-2010-07-295147","type":"journal-article","created":{"date-parts":[[2010,10,13]],"date-time":"2010-10-13T08:33:14Z","timestamp":1286958794000},"page":"647-650","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":36,"title":["Iron-deficiency anemia from matriptase-2 inactivation is dependent on the presence of functional Bmp6"],"prefix":"10.1182","volume":"117","author":[{"given":"Anne","family":"Lenoir","sequence":"first","affiliation":[{"name":"Institut Cochin, Universit\u00e9 Paris Descartes, Paris, France;"},{"name":"Inserm, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Deschemin","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 Paris Descartes, Paris, France;"},{"name":"Inserm, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9on","family":"Kautz","sequence":"additional","affiliation":[{"name":"Inserm, Toulouse, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Ramsay","sequence":"additional","affiliation":[{"name":"Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncolog\u00eda, Universidad de Oviedo, Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Paule","family":"Roth","sequence":"additional","affiliation":[{"name":"Inserm, Toulouse, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Lopez-Otin","sequence":"additional","affiliation":[{"name":"Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncolog\u00eda, Universidad de Oviedo, Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Vaulont","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 Paris Descartes, Paris, France;"},{"name":"Inserm, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00ebl","family":"Nicolas","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 Paris Descartes, Paris, France;"},{"name":"Inserm, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2019111723330112000_B1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev.physiol.69.031905.164337","article-title":"Iron homeostasis.","volume":"69","author":"Andrews","year":"2007","journal-title":"Annu Rev Physiol"},{"issue":"1","key":"2019111723330112000_B2","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/nrm2295","article-title":"Regulation of iron acquisition and storage: consequences for iron-linked disorders.","volume":"9","author":"De Domenico","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"10","key":"2019111723330112000_B3","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.biochi.2009.06.012","article-title":"Hepcidin, the iron watcher.","volume":"91","author":"Viatte","year":"2009","journal-title":"Biochimie"},{"issue":"4","key":"2019111723330112000_B4","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1182\/blood-2008-03-143354","article-title":"Iron regulates phosphorylation of Smad1\/5\/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver.","volume":"112","author":"Kautz","year":"2008","journal-title":"Blood"},{"issue":"5","key":"2019111723330112000_B5","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/ng1777","article-title":"Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression.","volume":"38","author":"Babitt","year":"2006","journal-title":"Nat Genet"},{"issue":"4","key":"2019111723330112000_B6","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/ng.320","article-title":"Lack of the bone morphogenetic protein BMP6 induces massive iron overload.","volume":"41","author":"Meynard","year":"2009","journal-title":"Nat Genet"},{"issue":"4","key":"2019111723330112000_B7","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/ng.335","article-title":"BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism.","volume":"41","author":"Andriopoulos","year":"2009","journal-title":"Nat Genet"},{"issue":"8","key":"2019111723330112000_B8","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1172\/JCI25049","article-title":"A mouse model of juvenile hemochromatosis.","volume":"115","author":"Huang","year":"2005","journal-title":"J Clin Invest"},{"issue":"6","key":"2019111723330112000_B9","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.cmet.2005.10.010","article-title":"A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression.","volume":"2","author":"Wang","year":"2005","journal-title":"Cell Metab"},{"issue":"5879","key":"2019111723330112000_B10","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1126\/science.1157121","article-title":"The serine protease TMPRSS6 is required to sense iron deficiency.","volume":"320","author":"Du","year":"2008","journal-title":"Science"},{"issue":"5","key":"2019111723330112000_B11","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/ng.130","article-title":"Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA).","volume":"40","author":"Finberg","year":"2008","journal-title":"Nat Genet"},{"issue":"6","key":"2019111723330112000_B12","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1182\/blood-2008-04-149773","article-title":"Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis.","volume":"112","author":"Folgueras","year":"2008","journal-title":"Blood"},{"issue":"6","key":"2019111723330112000_B13","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.cmet.2008.09.012","article-title":"The serine protease matriptase-2 (TMPRSS6) inhibits hepcidinactivation by cleaving membrane hemojuvelin.","volume":"8","author":"Silvestri","year":"2008","journal-title":"Cell Metab"},{"issue":"6","key":"2019111723330112000_B14","doi-asserted-by":"crossref","first-page":"840","DOI":"10.3324\/haematol.2008.001867","article-title":"Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis.","volume":"94","author":"Ramsay","year":"2009","journal-title":"Haematologica"},{"issue":"10","key":"2019111723330112000_B15","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.3324\/haematol.13724","article-title":"New and old players in the hepcidin pathway.","volume":"93","author":"Camaschella","year":"2008","journal-title":"Haematologica"},{"issue":"4","key":"2019111723330112000_B16","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1053\/j.seminhematol.2009.06.006","article-title":"Iron-refractory iron deficiency anemia.","volume":"46","author":"Finberg","year":"2009","journal-title":"Semin Hematol"},{"issue":"7","key":"2019111723330112000_B17","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1182\/blood-2005-10-4071","article-title":"Chronic hepcidin induction causes hyposideremia and alters the pattern of cellular iron accumulation in hemochromatotic mice.","volume":"107","author":"Viatte","year":"2006","journal-title":"Blood"},{"issue":"6","key":"2019111723330112000_B18","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1096\/fj.09-152561","article-title":"Oncostatin M is a potent inducer of hepcidin, the iron regulatory hormone.","volume":"24","author":"Chung","year":"2010","journal-title":"FASEB J"},{"issue":"18","key":"2019111723330112000_B19","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.1182\/blood-2009-05-224808","article-title":"Down-regulation of Bmp\/Smad signaling by Tmprss6 is required for maintenance of systemic iron homeostasis.","volume":"115","author":"Finberg","year":"2010","journal-title":"Blood"},{"issue":"4","key":"2019111723330112000_B20","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1111\/j.1365-2141.2009.07873.x","article-title":"Suppression of the hepcidin-encoding gene Hamp permits iron overload in mice lacking both hemojuvelin and matriptase-2\/TMPRSS6.","volume":"147","author":"Truksa","year":"2009","journal-title":"Br J Haematol"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/117\/2\/647\/1338006\/zh800211000647.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/117\/2\/647\/1338006\/zh800211000647.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T04:33:17Z","timestamp":1574051597000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/117\/2\/647\/28120\/Irondeficiency-anemia-from-matriptase2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1,13]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2011,1,13]]}},"URL":"https:\/\/doi.org\/10.1182\/blood-2010-07-295147","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1,13]]}}}