Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs)
Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs)
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DOI：
10.1172/jci31370
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发表时间：
2007-07-01
影响因子：
15.9
通讯作者：
Johnson, Randall S.
中科院分区：
文献类型：
--
作者：
Peyssonnaux, Carole;Zinkernagel, Annelies S.;Johnson, Randall S.
铁对许多生物过程至关重要，包括氧气输送，其供应受到严格管制。铁调素是一种在肝脏中合成的小肽，是哺乳动物铁吸收和体内平衡的关键调节剂。铁调素的产生增加铁超载和减少贫血和缺氧，但管理铁调素对这些刺激的反应的分子机制尚不清楚。在这里，我们建立了von Hippel-Lindau/低氧诱导转录因子（VHL/HIF）通路是体内铁稳态和铁调素调节之间的重要联系。通过铁调素的协同下调和促红细胞生成素和膜铁转运蛋白的协同上调，VHL-HIF途径动员铁以支持红细胞产生。
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.