Hepcidin is a major regulator of iron homeostasis, and its expression in liver is regulated by iron, inflammation and erythropoietic activity with mechanisms that involve bone morphogenetic proteins (BMPs) binding their receptors and co-receptors. Here we show that exogenous heparin strongly inhibited hepcidin expression in hepatic HepG2 cells at pharmacological concentrations, with a mechanism that probably involves BMP6 sequestering and the blocking of SMAD signaling. Treatment of mice with pharmacological doses of heparin inhibited liver hepcidin mRNA expression and SMAD phosphorylation, reduced spleen iron concentration while increasing serum iron. Moreover, we observed a strong reduction of serum hepcidin in five patients treated with heparin to prevent deep vein thrombosis and this was accompanied by an increase of serum iron and a reduction of C-reactive protein levels. The data show an unrecognised role of heparin in regulating iron homeostasis and indicate novel approaches to the treatment of of iron restricted iron deficiency anemia.

Heparin: a potent inhibitor of hepcidin expression in vitro and in vivo

GIRELLI, Domenico;CAMPOSTRINI, Natascia;
2011-01-01

Abstract

Hepcidin is a major regulator of iron homeostasis, and its expression in liver is regulated by iron, inflammation and erythropoietic activity with mechanisms that involve bone morphogenetic proteins (BMPs) binding their receptors and co-receptors. Here we show that exogenous heparin strongly inhibited hepcidin expression in hepatic HepG2 cells at pharmacological concentrations, with a mechanism that probably involves BMP6 sequestering and the blocking of SMAD signaling. Treatment of mice with pharmacological doses of heparin inhibited liver hepcidin mRNA expression and SMAD phosphorylation, reduced spleen iron concentration while increasing serum iron. Moreover, we observed a strong reduction of serum hepcidin in five patients treated with heparin to prevent deep vein thrombosis and this was accompanied by an increase of serum iron and a reduction of C-reactive protein levels. The data show an unrecognised role of heparin in regulating iron homeostasis and indicate novel approaches to the treatment of of iron restricted iron deficiency anemia.
2011
Hepcidin; iron homeostasis; anemia; heparin; inflammation
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/346276
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