|
|
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.
 Previous Article | Next Article 
Submitted March 6, 2008
Accepted May 19, 2008
Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver
Leon Kautz, Delphine Meynard, Annabelle Monnier, Valerie Darnaud, Regis Bouvet, Rui-Hong Wang, Chiuxia Deng, Sophie Vaulont, Jean Mosser, Helene Coppin, and Marie-Paule Roth*
U563, Inserm, Toulouse, France
Universite Toulouse III Paul-Sabatier, IFR 30, Toulouse, France
UMR6061, CNRS, Rennes, France
Service de Genomique Medicale, CHU, Rennes, France
GDDB NIDDKD, NIH, Bethesda, United States
U567, Inserm, Paris, France
* Corresponding author; email: roth{at}cict.fr.
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 two genetic backgrounds fed iron-deficient, -balanced, or -enriched diets. Among 1419 transcripts significantly modulated by the dietary iron content, four were regulated similarly to the hepcidin genes Hamp1 and Hamp2. They are coding for Bmp6, Smad7, Id1, and Atoh8 that are 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]
|
|
|
|
|
