Hepcidin: A Critical Regulator of Iron Metabolism during Hypoxia

Figure 2

Pathways for hypoxia-mediated hepcidin regulation. Hypoxia or hypoxia mimetics result in HIF-1α accumulation. HIF-1α has been proposed to be a direct, negative regulator of hepcidin by binding to putative HIF response elements (HRE) in the hepcidin promoter [38]. Expression of the hemojuvelin cleaving enzymes TMPRSS6 and furin is increased by hypoxia via HIF-1α [53, 55]. Hemojuvelin cleavage results in decreased hepcidin promoter activation through inhibition of BMP/bone morphogenetic response element (BRE) signaling [44]. Localized, adipocyte hypoxia caused by central obesity results in elevated IL-6 levels which can increase hepatocyte hepcidin expression via the STAT3 binding site [75].