Non-Anticoagulant Heparins Are Hepcidin Antagonists for the Treatment of Anemia
AbstractThe peptide hormone hepcidin is a key controller of systemic iron homeostasis, and its expression in the liver is mainly regulated by bone morphogenetic proteins (BMPs), which are heparin binding proteins. In fact, heparins are strong suppressors of hepcidin expression in hepatic cell lines that act by inhibiting the phosphorylation of SMAD1/5/8 proteins elicited by the BMPs. The inhibitory effect of heparins has been demonstrated in cells and in mice, where subcutaneous injections of non-anticoagulant heparins inhibited liver hepcidin expression and increased iron bioavailability. The chemical characteristics for high anti-hepcidin activity in vitro and in vivo include the 2O-and 6O-sulfation and a molecular weight above 7 kDa. The most potent heparins have been found to be the super-sulfated ones, active in hepcidin suppression with a molecular weight as low as 4 kDa. Moreover, the alteration of endogenous heparan sulfates has been found to cause a reduction in hepcidin expression in vitro and in vivo, indicating that heparins act by interfering with the interaction between BMPs and components of the complex involved in the activation of the BMP/SMAD1/5/8 pathway. This review summarizes recent findings on the anti-hepcidin activity of heparins and their possible use for the treatment of anemia caused by hepcidin excess, including the anemia of chronic diseases. View Full-Text
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Poli, M.; Asperti, M.; Ruzzenenti, P.; Naggi, A.; Arosio, P. Non-Anticoagulant Heparins Are Hepcidin Antagonists for the Treatment of Anemia. Molecules 2017, 22, 598.
Poli M, Asperti M, Ruzzenenti P, Naggi A, Arosio P. Non-Anticoagulant Heparins Are Hepcidin Antagonists for the Treatment of Anemia. Molecules. 2017; 22(4):598.Chicago/Turabian Style
Poli, Maura; Asperti, Michela; Ruzzenenti, Paola; Naggi, Annamaria; Arosio, Paolo. 2017. "Non-Anticoagulant Heparins Are Hepcidin Antagonists for the Treatment of Anemia." Molecules 22, no. 4: 598.
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