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Blood, 17 September 2009, Vol. 114, No. 12, pp. 2515-2520. Prepublished online as a Blood First Edition Paper on July 21, 2009; DOI 10.1182/blood-2009-02-206771. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2009-02-206771v1 114/12/2515    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Kautz, L. Articles by Roth, M.-P. PubMed PubMed Citation Articles by Kautz, L. Articles by Roth, M.-P. Related Collections Red Cells, Iron, and Erythropoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS, IRON, AND ERYTHROPOIESIS BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression Léon Kautz1,2, Delphine Meynard1,2, Céline Besson-Fournier1,2, Valérie Darnaud1,2, Talal Al Saati1,2, Hélène Coppin1,2,*, and Marie-Paule Roth1,2,* 1 Inserm, U563, Toulouse; and 2 Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan and Institut Biomédical de Toulouse, Toulouse, France Impaired regulation of hepcidin expression in response to iron loading appears to be the pathogenic mechanism for hereditary hemochromatosis. Iron normally induces expression of the BMP6 ligand, which, in turn, activates the BMP/Smad signaling cascade directing hepcidin expression. The molecular function of the HFE protein, involved in the most common form of hereditary hemochromatosis, is still unknown. We have used Hfe-deficient mice of different genetic backgrounds to test whether HFE has a role in the signaling cascade induced by BMP6. At 7 weeks of age, these mice have accumulated iron in their liver and have increased Bmp6 mRNA and protein. However, in contrast to mice with secondary iron overload, levels of phosphorylated Smads 1/5/8 and of Id1 mRNA, both indicators of BMP signaling, are not significantly higher in the liver of these mice than in wild-type livers. As a consequence, hepcidin mRNA levels in Hfe-deficient mice are similar or marginally reduced, compared with 7-week-old wild-type mice. The inappropriately low levels of Id1 and hepcidin mRNA observed at weaning further suggest that Hfe deficiency triggers iron overload by impairing hepatic Bmp/Smad signaling. HFE therefore appears to facilitate signal transduction induced by the BMP6 ligand. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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