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Proposed role of nonanticoagulant heparins as hepcidin production inhibitors. Nonanticoagulant heparins bind to BMP ligands to prevent their interaction with BMP type I (BMP-RI) and BMP type II (BMP-RII) receptors and the coreceptor hemojuvelin on the hepatocyte membrane. Blockade of this active signaling complex inhibits phosphorylation of intracellular SMAD 1, SMAD5, and SMAD8 proteins (SMAD1/5/8) and their interaction with SMAD4, thereby blunting hepcidin transcription.
