BMP / Smad signaling is not enhanced in Hfe - deficient mice despite increased

BMP / Smad signaling is not enhanced in Hfe - deficient mice despite increased Bmp 6 e xpression Running title : Bmp / Smad signaling defect in hemochromatotic mice

BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression.

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 stil...

RED CELLS, IRON, AND ERYTHROPOIESIS BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression

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 stil...

Tmprss6 is a genetic modifier of the Hfe-hemochromatosis phenotype in mice.

The hereditary hemochromatosis protein HFE promotes the expression of hepcidin, a circulating hormone produced by the liver that inhibits dietary iron absorption and macrophage iron release. HFE mutations are associated with impaired hepatic bone morphogenetic protein (BMP)/SMAD signaling for hepcidin production. TMPRSS6, a transmembrane serine protease mutated in iron-refractory iron deficienc...

Down-regulation of Bmp/Smad signaling by Tmprss6 is required for maintenance of systemic iron homeostasis.

Iron-refractory, iron-deficiency anemia (IRIDA) is a familial disorder characterized by iron deficiency anemia unresponsive to oral iron treatment but partially responsive to intravenous iron therapy. Previously, we showed that IRIDA patients harbor loss-of-function mutations in TMPRSS6, a type II transmembrane serine protease primarily expressed by the liver. Both humans and mice with TMPRSS6 ...