Iron metabolism: State of the art
Iron metabolism: State of the art
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DOI：
10.1016/j.tracli.2017.06.015
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发表时间：
2017-09-01
影响因子：
1.7
通讯作者：
Karim, Z.
中科院分区：
文献类型：
--
作者：
Daher, R.;Karim, Z.
铁的体内平衡依赖于肠道的吸收量和储存部位巨噬细胞的释放量。铁稳态也取决于用于红细胞生成的铁的量。铁调素主要由肝脏合成，是铁代谢的主要调节剂。铁调素通过抑制铁输出体，铁转运蛋白表达的两个组织，肠和巨噬细胞降低血清铁。此外，在肠上皮细胞中，铁调素通过作用于顶端转运蛋白DMT 1来抑制铁内流。铁调素表达缺陷导致实质铁超载的出现可能是遗传性的或继发于红细胞生成不良。对遗传性血色病的探索揭示了几个基因的参与，包括最近描述的BMP 6。非输血性继发性血色素沉着症是由于铁调素被细胞因子抑制，特别是由红细胞前体直接产生的红细胞铁酮因子。铁过载与称为NTBI的游离形式的铁的出现相关。NTBI的流入似乎是由肝脏中的ZIP14转运蛋白和心肌细胞中的钙通道介导的。除肝脏外，铁调素在几种肝外组织中表达程度较低，在肝外组织中，铁调素发挥其抗微生物肽的祖先作用。在肾脏中，铁调素调节针对尿路感染的防御屏障。在心脏中，铁调素通过自分泌调节心肌细胞表面铁蛋白表达来维持组织铁稳态。总之，铁调素仍然是一个有前途的治疗工具，在各种铁病理。(C)2017年Elsevier Masson SAS。All rights reserved.
Iron homeostasis relies on the amount of its absorption by the intestine and its release from storage sites, the macrophages. Iron homeostasis is also dependent on the amount of iron used for the erythropoiesis. Hepcidin, which is synthesized predominantly by the liver, is the main regulator of iron metabolism. Hepcidin reduces serum iron by inhibiting the iron exporter, ferroportin expressed both tissues, the intestine and the macrophages. In addition, in the enterocytes, hepcidin inhibits the iron influx by acting on the apical transporter, DMT1. A defect of hepcidin expression leading to the appearance of a parenchymal iron overload may be genetic or secondary to dyserythropoiesis. The exploration of genetic hemochromatosis has revealed the involvement of several genes, including the recently described BMP6. Non-transfusional secondary hemochromatosis is due to hepcidin repression by cytokines, in particular the erythroferone factor that is produced directly by the erythroid precursors. Iron overload is correlated with the appearance of a free form of iron called NTBI. The influx of NTBI seems to be mediated by ZIP14 transporter in the liver and by calcium channels in the cardiomyocytes. Beside the liver, hepcidin is expressed at lesser extent in several extrahepatic tissues where it plays its ancestral role of antimicrobial peptide. In the kidney, hepcidin modulates defense barriers against urinary tract infections. In the heart, hepcidin maintains tissue iron homeostasis by an autocrine regulation of ferroprotine expression on the surface of cardiomyocytes. In conclusion, hepcidin remains a promising therapeutic tool in various iron pathologies. (C) 2017 Elsevier Masson SAS. All rights reserved.