Scheme of iron homeostasis and hepcidin regulation in hypoxia. Systemic hypoxia/iron deficiency stabilizes HIF-1α, which may activate/inhibit the HIF-1α target genes. Among these, furin is up-regulated, while hepcidin is down-regulated. The inhibition of hepcidin increases iron absorption. Up-regulation of furin via HIF-1α may occur in hypoxic skeletal muscles (bold line) and increase s-HJV production. s-HJV, sequestering BMP2/4, blocks hepcidin activation mediated by the m-HJV/BMPs complex (dotted line) in the hepatocytes. At the same time, furin may cleave m-HJV to reduce the BMP coreceptor.