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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1503-1509. Prepublished online as a Blood First Edition Paper on June 6, 2008; DOI 10.1182/blood-2008-03-143354. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2008-03-143354v1 112/4/1503    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kautz, L. Articles by Roth, M.-P. Search for Related Content PubMed PubMed Citation Articles by Kautz, L. Articles by Roth, M.-P. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver Léon Kautz1,2,*, Delphine Meynard1,2,*, Annabelle Monnier3,4, Valérie Darnaud1,2, Régis Bouvet5, Rui-Hong Wang6, Chiuxia Deng6, Sophie Vaulont7,8, Jean Mosser3,5,9, Hélène Coppin1,2,, and Marie-Paule Roth1,2, 1 Institut National de la Santé et de la Recherche Médicale (Inserm), U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France; 2 Université Toulouse III Paul-Sabatier, Institut Fédératif de Recherche 30 (IFR 30), Toulouse, France; 3 Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche 6061 (UMR6061), Institut de Génétique et Développement, and 4 CNRS (UMR6553), Ecobio, Université de Rennes 1, Rennes, France; 5 Service de Génomique Médicale, Centre Hospitalier Universitaire (CHU) de Rennes, Rennes, France; 6 Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; 7 Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France; 8 Inserm, U567, Paris, France; and 9 Plate-forme transcriptome OUEST-genopole, Rennes, France Although hepcidin expression was shown to be induced by the BMP/Smad signaling pathway, it is not yet known how iron regulates this pathway and what its exact molecular targets are. We therefore assessed genome-wide liver transcription profiles of mice of 2 genetic backgrounds fed iron-deficient, -balanced, or -enriched diets. Among 1419 transcripts significantly modulated by the dietary iron content, 4 were regulated similarly to the hepcidin genes Hamp1 and Hamp2. They are coding for Bmp6, Smad7, Id1, and Atoh8 all related to the Bmp/Smad pathway. As shown by Western blot analysis, variations in Bmp6 expression induced by the diet iron content have for functional consequence similar changes in Smad1/5/8 phosphorylation that leads to formation of heteromeric complexes with Smad4 and their translocation to the nucleus. Gene expression variations induced by secondary iron deficiency or iron overload were compared with those consecutive to Smad4 and Hamp1 deficiency. Iron overload developed by Smad4- and Hamp1-deficient mice also increased Bmp6 transcription. However, as shown by analysis of mice with liver-specific disruption of Smad4, activation of Smad7, Id1, and Atoh8 transcription by iron requires Smad4. This study points out molecules that appear to play a critical role in the control of systemic iron balance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Kautz, D. Meynard, C. Besson-Fournier, V. Darnaud, T. Al Saati, H. Coppin, and M.-P. Roth BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression Blood, September 17, 2009; 114(12): 2515 - 2520. [Abstract] [Full Text] [PDF] A.-S. Zhang, F. Yang, J. Wang, H. Tsukamoto, and C. A. Enns Hemojuvelin-Neogenin Interaction Is Required for Bone Morphogenic Protein-4-induced Hepcidin Expression J. Biol. Chem., August 21, 2009; 284(34): 22580 - 22589. [Abstract] [Full Text] [PDF] T. Tanno, P. Porayette, O. Sripichai, S.-J. Noh, C. Byrnes, A. Bhupatiraju, Y. T. Lee, J. B. Goodnough, O. Harandi, T. Ganz, et al. Identification of TWSG1 as a second novel erythroid regulator of hepcidin expression in murine and human cells Blood, July 2, 2009; 114(1): 181 - 186. [Abstract] [Full Text] [PDF] A. J. Ramsay, J. D. Hooper, A. R. Folgueras, G. Velasco, and C. Lopez-Otin Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis Haematologica, June 1, 2009; 94(6): 840 - 849. [Abstract] [Full Text] [PDF] G. Ramey, J.-C. Deschemin, and S. Vaulont Cross-talk between the mitogen activated protein kinase and bone morphogenetic protein/hemojuvelin pathways is required for the induction of hepcidin by holotransferrin in primary mouse hepatocytes Haematologica, June 1, 2009; 94(6): 765 - 772. [Abstract] [Full Text] [PDF] A. Iolascon, L. De Falco, and C. Beaumont Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis Haematologica, March 1, 2009; 94(3): 395 - 408. [Abstract] [Full Text] [PDF] M. D. Fleming The Regulation of Hepcidin and Its Effects on Systemic and Cellular Iron Metabolism Hematology, January 1, 2008; 2008(1): 151 - 158. [Abstract] [Full Text] [PDF]

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