Iron regulatory proteins are essential for intestinal function and control key iron absorption molecules in the duodenum
Iron regulatory proteins are essential for intestinal function and control key iron absorption molecules in the duodenum
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DOI：
10.1016/j.cmet.2007.10.006
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发表时间：
2008-01-01
期刊：
影响因子：
29
通讯作者：
Hentze, Matthias W.
中科院分区：
文献类型：
--
作者：
Galy, Bruno;Ferring-Appel, Dunja;Hentze, Matthias W.
铁调节蛋白（IRP）在细胞水平上协调关键铁代谢蛋白的转录后调节。与双IRP缺陷小鼠的胚胎致死相关的IRP 1和IRP 2之间的冗余已经排除了体内IRP功能的研究。在这里，我们使用Cre/Lox技术来产生在单个组织（肠）中缺乏IRP表达的活生物体。缺乏肠道IRP表达的小鼠出生后出现肠道吸收不良和脱水，并在出生后4周内死亡。我们证明，IRP控制二价金属转运蛋白1（DMT 1）的mRNA和蛋白质的表达，限制肠道铁进口商。IRP也被证明是至关重要的，以确保生理水平的基底外侧铁输出ferroportin。因此，IRP对于肠功能和生物体存活是必不可少的，并协调十二指肠中关键铁代谢蛋白的合成。
Iron regulatory proteins (IRPs) orchestrate the posttranscriptional regulation of critical iron metabolism proteins at the cellular level. Redundancy between IRP1 and IRP2 associated with embryonic lethality of doubly IRP-deficient mice has precluded the study of IRP function in vivo. Here we use Cre/Lox technology to generate viable organisms lacking IRP expression in a single tissue, the intestine. Mice lacking intestinal IRP expression develop intestinal malabsorption and dehydration postnatally and die within 4 weeks of birth. We demonstrate that IRPs control the expression of divalent metal transporter 1 (DMT1) mRNA and protein, a limiting intestinal iron importer. IRPs are also shown to be critically important to secure physiological levels of the basolateral iron exporter ferroportin. IRPs are thus essential for intestinal function and organismal survival and coordinate the synthesis of key iron metabolism proteins in the duodenum.