Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 117, Issue 7, Pages 1926-1932Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI31370
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Funding
- NCI NIH HHS [R01 CA100787] Funding Source: Medline
- NIAID NIH HHS [R01 AI060840, AI060840] Funding Source: Medline
- NIDDK NIH HHS [R21 DK073467] Funding Source: Medline
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Iron is essential for many biological processes, including oxygen delivery, and its supply is tightly regulated. Hepcidin, a small peptide synthesized in the liver, is a key regulator of iron absorption and homeostasis in mammals. Hepcidin production is increased by iron overload and decreased by anemia and hypoxia; but the molecular mechanisms that govern the hepcidin response to these stimuli are not known. Here we establish that the von Hippel-Lindau/hypoxia-inducible transcription factor (VHL/HIF) pathway is an essential link between iron homeostasis and hepcidin regulation in vivo. Through coordinate downregulation of hepcidin and upregulation of erythropoietin and ferroportin, the VHL-HIF pathway mobilizes iron to support erythrocyte production.
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