Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency.
Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency.
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DOI：
10.1016/j.cmet.2008.12.012
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发表时间：
2009-02
期刊：
影响因子：
29
通讯作者：
Gonzalez FJ
中科院分区：
文献类型：
--
作者：
Shah YM;Matsubara T;Ito S;Yim SH;Gonzalez FJ
缺铁和铁超载是世界上最普遍的营养失调。十二指肠细胞色素b （DcytB）和二价金属转运蛋白1 （DMT1）是铁吸收的调节因子。它们的表达在系统对铁的高需求期间增加，但调节DcytB和DMT1表达的分子机制尚不明确。十二指肠急性缺铁后，肠内缺氧诱导因子（HIF）信号被诱导，导致DcytB和DMT1表达激活，铁摄取增加。DcytB和DMT1是HIF-2α的直接靶基因。肠道中HIF信号的遗传破坏消除了铁缺乏后对铁吸收的适应性诱导，导致全身铁含量低和血液系统缺陷。这些结果表明，肠道中的HIF信号是系统铁稳态的关键调节因子。
Iron deficiency and iron overload are among the most prevalent nutritional disorders worldwide. Duodenal cytochrome b (DcytB) and divalent metal transporter 1 (DMT1) are regulators of iron absorption. Their expression is increased during high systemic requirements for iron, but the molecular mechanisms that regulate DcytB and DMT1 expression are undefined. Hypoxia inducible factor (HIF) signaling was induced in the intestine following acute iron deficiency in the duodenum, resulting in activation of DcytB and DMT1 expression and an increase in iron uptake. DcytB and DMT1 were demonstrated as direct HIF-2α target genes. Genetic disruption of HIF signaling in the intestine abolished the adaptive induction of iron absorption following iron deficiency, resulting in low systemic iron and hematological defects. These results demonstrate that HIF signaling in the intestine is a critical regulator of systemic iron homeostasis.
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