Iron Regulatory Proteins Control a Mucosal Block to Intestinal Iron Absorption
Iron Regulatory Proteins Control a Mucosal Block to Intestinal Iron Absorption
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DOI：
10.1016/j.celrep.2013.02.026
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发表时间：
2013-03-01
期刊：
影响因子：
8.8
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.
哺乳动物的铁代谢受铁调素的系统调节，而铁调节蛋白（IRP）则在细胞内协调转录后调节网络。通过对成年小鼠肠上皮中的两种IRP进行配体诱导的基因消融，我们证明IRP缺乏会损害铁的吸收，并通过铁蛋白介导的“粘膜阻断”促进粘膜铁的保留。“我们表明，IRP缺乏不会干扰肠道对身体铁负荷和红细胞生成铁需求的感知，而是改变了铁吸收机制的基础表达。因此，IRP通过限制铁蛋白“粘膜阻断”来确保足够的铁转运穿过吸收性肠上皮细胞，并定义铁吸收的基础设定点，在该基础设定点上覆盖IRP非依赖性系统调节输入。
Mammalian iron metabolism is regulated systemically by the hormone hepcidin and cellularly by iron regulatory proteins (IRPs) that orchestrate a post-transcriptional regulatory network. Through ligand-inducible genetic ablation of both IRPs in the gut epithelium of adult mice, we demonstrate that IRP deficiency impairs iron absorption and promotes mucosal iron retention via a ferritin-mediated "mucosal block." We show that IRP deficiency does not interfere with intestinal sensing of body iron loading and erythropoietic iron need, but rather alters the basal expression of the iron-absorption machinery. IRPs thus secure sufficient iron transport across absorptive enterocytes by restricting the ferritin "mucosal block" and define a basal set point for iron absorption upon which IRP-independent systemic regulatory inputs are overlaid.