Smad6 and Smad7 are co-regulated with hepcidin in mouse models of iron overload


The inhibitory Smad7 acts as a critical suppressor of hepcidin, the major regulator of systemic iron homeostasis. In this study we define the mRNA expression of the two functionally related Smad proteins, Smad6 and Smad7, within pathways known to regulate hepcidin levels. Using mouse models for hereditary hemochromatosis (Hfe-, TfR2-, Hfe/TfR2-, Hjv- and hepcidin1-deficient mice) we show that hepcidin, Smad6 and Smad7 mRNA expression is coordinated in such a way that it correlates with the activity of the Bmp/Smad signaling pathway rather than with liver iron levels. This regulatory circuitry is disconnected by iron treatment of Hfe-/- and Hfe/TfR2 mice that significantly increases hepatic iron levels as well as hepcidin, Smad6 and Smad7 mRNA expression but fails to augment pSmad1/5/8 levels. This suggests that additional pathways contribute to the regulation of hepcidin, Smad6 and Smad7 under these conditions which do not require Hfe.


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Biochim. Biophys. Acta
Biochim. Biophys. Acta 1832(1): 76-84
11th Sep 2012

Maja Vujić Spasić, Richard Sparla, Katarzyna Mleczko-Sanecka, Mary C Migas, Katja Breitkopf-Heinlein, Steven Dooley, Sophie Vaulont, Robert E Fleming, Martina U Muckenthaler

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[Katja Breitkopf-Heinlein] [Steven Dooley] [Martina Muckenthaler]

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Views: 2221
  • Created: 31st Oct 2012 at 09:07
  • Last updated: 24th Oct 2013 at 16:15

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