Systemic regulation of Hephaestin and Ireg1 revealed in studies of genetic and nutritional iron deficiency
Systemic regulation of Hephaestin and Ireg1 revealed in studies of genetic and nutritional iron deficiency
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DOI：
10.1182/blood-2003-02-0347
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发表时间：
2003-09-01
期刊：
影响因子：
20.3
通讯作者：
Vulpe, CD
中科院分区：
文献类型：
--
作者：
Chen, HJ;Su, T;Vulpe, CD
铁黄素是一种膜结合的多铜铁氧化酶，是铁从肠上皮细胞进入循环所必需的。性连锁贫血（sla）小鼠具有突变形式的肝啡肽和肠基底外侧铁转运缺陷，导致缺铁和贫血。lreg 1（SLC 11 A3，也称为Ferroportin 1或Mtp 1）是假定的肠基底外侧铁转运蛋白。我们比较了sla小鼠和C57 BL/6 J小鼠的铁水平和参与铁摄取和储存的基因表达，这些小鼠喂食缺铁、铁过载或对照饮食。与对照组相比，缺铁野生型小鼠和SLA小鼠的Heph和Ireg 1 mRNA表达均增加，而只有缺铁野生型小鼠的刷状缘转运蛋白Dmt 1表达增加。与缺铁小鼠不同，sla小鼠肠细胞积累非血红素铁和铁蛋白。这些结果表明，Dmt 1可以通过肠上皮细胞铁水平进行调节，而Hephaestin和Ireg 1的表达响应于系统性而不是局部的铁状态信号。因此，基底外侧转运步骤似乎是小肠对机体铁需求变化作出反应的主要部位。
Hephaestin is a membrane-bound multicopper ferroxidase necessary for iron egress from intestinal enterocytes into the circulation. Mice with sex-linked anemia (sla) have a mutant form of Hephaestin and a defect in intestinal basolateral iron transport, which results in iron deficiency and anemia. lreg1 (SLC11A3, also known as Ferroportin1 or Mtp1) is the putative intestinal basolateral iron transporter. We compared iron levels and expression of genes involved in iron uptake and storage in sla mice and C57BL/6J mice fed iron-deficient, iron-overload, or control diets. Both iron-deficient wildtype mice and sla mice showed increased expression of Heph and Ireg1 mRNA, compared to controls, whereas only iron-deficient wild-type mice had increased expression of the brush border transporter Dmt1. Unlike iron-deficient mice, sla mouse enterocytes accumulated non-heme iron and ferritin. These results indicate that Dmt1 can be modulated by the enterocyte iron level, whereas Hephaestin and Ireg1 expression respond to systemic rather than local signals of iron status. Thus, the basolateral transport step appears to be the primary site at which the small intestine responds to alterations in body iron requirements.