{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T13:47:07Z","timestamp":1764510427410},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,3,26]],"date-time":"2012-03-26T00:00:00Z","timestamp":1332720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">SMAD<\/jats:styled-content> signalling pathway plays an important role in iron homeostasis, regulating hepcidin expression in response to body iron levels. However, the role of this pathway in the reduction in hepcidin associated with increased erythropoiesis (and secondary iron loading) is unclear. To investigate this, we established a mouse model of chronic stimulated erythropoiesis with secondary iron loading using the haemolytic agent phenylhydrazine. We then examined the expression of components of the <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>6\/<jats:styled-content style=\"fixed-case\">SMAD<\/jats:styled-content> signalling pathway in these animals. We also examined this pathway in the <jats:styled-content style=\"fixed-case\"><jats:italic>Hbb<jats:sup>th3\/+<\/jats:sup><\/jats:italic><\/jats:styled-content> mouse, a model of the iron loading anaemia \u03b2\u2010thalassaemia intermedia. Increasing doses of phenylhydrazine led to a progressive increase in both liver iron levels and <jats:styled-content style=\"fixed-case\"><jats:italic>Bmp6<\/jats:italic> mRNA<\/jats:styled-content> expression, but, in contrast, hepatic <jats:styled-content style=\"fixed-case\"><jats:italic>Hamp<\/jats:italic><\/jats:styled-content> expression declined. The increase in <jats:styled-content style=\"fixed-case\"><jats:italic>Bmp6<\/jats:italic><\/jats:styled-content> expression was not associated with a corresponding change in the phosphorylation of hepatic <jats:styled-content style=\"fixed-case\">SMAD<\/jats:styled-content>1\/5\/8, indicating that stimulated erythropoiesis decreases the ability of <jats:styled-content style=\"fixed-case\"><jats:roman>BMP6<\/jats:roman><\/jats:styled-content> to alter <jats:styled-content style=\"fixed-case\">SMAD<\/jats:styled-content> phosphorylation. Increased erythropoiesis also reduces the capacity of phosphorylated <jats:styled-content style=\"fixed-case\">SMAD<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">pSMAD<\/jats:styled-content>) to induce hepcidin, as <jats:styled-content style=\"fixed-case\"><jats:italic>Hamp<\/jats:italic><\/jats:styled-content> levels declined despite no changes in <jats:styled-content style=\"fixed-case\">pSMAD<\/jats:styled-content>1\/5\/8. Similar results were seen in <jats:styled-content style=\"fixed-case\"><jats:italic>Hbb<jats:sup>th3\/+<\/jats:sup><\/jats:italic><\/jats:styled-content> mice. Thus the erythroid signal probably affects some components of <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">SMAD<\/jats:styled-content> signalling, but also may exert some independent effects.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2012.09104.x","type":"journal-article","created":{"date-parts":[[2012,3,27]],"date-time":"2012-03-27T00:39:38Z","timestamp":1332808778000},"page":"615-626","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Stimulated erythropoiesis with secondary iron loading leads to a decrease in hepcidin despite an increase in bone morphogenetic protein 6 expression"],"prefix":"10.1111","volume":"157","author":[{"given":"David M.","family":"Frazer","sequence":"first","affiliation":[{"name":"Iron Metabolism Laboratory Queensland Institute of Medical Research Brisbane Qld 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