Direct modulation of hepatocyte hepcidin signaling by iron

Figure 7 Scheme of iron-mediated blockage of hepcidin transcription via bone morphogenetic protein/small mothers against decapentaplegic but independent of signal transducer and activator of transcription 3 signaling. Iron (ferric ammonium citrate) primarily blocks hepcidin transcription via the bone morphogenetic protein (BMP)/small mothers against decapentaplegic pathway while no effect on signal transducer and activator of transcription 3 signaling was observed. The scheme also shows all studied hepcidin signaling pathways including BMP6, interleukin (IL)-6, IL-1β, hypoxia or a complex co-culture model with macrophages. IL-1β: Interleukin 1β; IL-6: Interleukin 6; BMP6: Bone morphogenetic protein 6; FAC: Ferric ammonium citrate; IL-1R: IL-1 receptor; IL-6R: IL-6 receptor: NOX4: NADPH Oxidase 4; BMPR: BMP receptor; p-STAT3: Phosphorylated signal transducer and activator of transcription 3; p-SMAD1/5/8: Phosphorylated small mothers against decapentaplegic 1/5/8.