The orchestration of body iron intake: how and where do enterocytes receive their cues?
The orchestration of body iron intake: how and where do enterocytes receive their cues?
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DOI：
10.1016/s1079-9796(03)00039-1
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发表时间：
2003-05-01
影响因子：
2.3
通讯作者：
Anderson, GJ
中科院分区：
文献类型：
--
作者：
Frazer, DM;Anderson, GJ
近年来，我们对铁如何穿过肠上皮的了解有了很大提高，尽管体内铁需求调节这一过程的机制仍然知之甚少。通过批判性地研究这一领域的早期文献，并结合最近的进展，我们制定了一个模型，解释了铁的吸收如何受到身体铁需求的调节。特别是，该分析表明，改变吸收的信号对成熟的肠上皮细胞产生直接影响，而不是影响肠隐窝细胞。我们建议，肝脏中起着核心作用，通过调节铁调素的表达，在铁稳态的维持中响应于二铁转铁蛋白在循环中的转铁蛋白受体1的水平的比例的变化。运铁蛋白受体2和HFE/运铁蛋白受体I复合物检测到这种变化。然后，循环铁调素直接影响Ireg 1在十二指肠成熟绒毛肠细胞中的表达，从而调节响应于身体铁需求的铁吸收。以这种方式，身体可以通过调节从十二指肠上皮细胞和可能的网状内皮系统的巨噬细胞释放铁来快速和适当地响应铁需求的变化。该模型可以解释正常条件下铁吸收的调节，以及在病理状态如血色素沉着症和地中海贫血中观察到的不适当吸收。(C)2003 Elsevier Science（美国）。All rights reserved.
Our understanding of how iron transverses the intestinal epithelium has improved greatly in recent years, although the mechanism by which body iron demands regulate this process remains poorly understood. By critically examining the earlier literature in this field and considering it in combination with recent advances we have formulated a model explaining how iron absorption could be regulated by body iron requirements. In particular, this analysis suggests that signals to alter absorption exert a direct effect on mature enterocytes rather than influencing the intestinal crypt cells. We propose that the liver plays a central role in the maintenance of iron homeostasis by regulating the expression of hepcidin in response to changes in the ratio of diferric transferrin in the circulation to the level of transferrin receptor 1. Such changes are detected by transferrin receptor 2 and the HFE/transferrin receptor I complex. Circulating hepcidin then directly influences the expression of Ireg1 in the mature villus enterocytes of the duodenum, thereby regulating iron absorption in response to body iron requirements. In this manner, the body can rapidly and appropriately respond to changes in iron demands by adjusting the release of iron from the duodenal enterocytes and, possibly, the macrophages of the reticuloendothelial system. This model can explain the regulation of iron absorption under normal conditions and also the inappropriate absorption seen in pathological states such as hemochromatosis and thalassemia. (C) 2003 Elsevier Science (USA). All rights reserved.