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

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...

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

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 ...

Liver and serum iron: discrete regulators of hepatic hepcidin expression.

T o prevent pathological excesses or deficiencies, body iron balance must be tightly controlled due to the lack of a highly evolved mechanism for iron excretion. This is achieved through the liver peptide hepcidin, which efficiently regulates the processes of duodenal iron absorption, macrophage iron release and tissue iron storage, primarily in the liver. Hepcidin is released into the circulat...