Hepcidin and iron homeostasis.
Hepcidin and iron homeostasis.
复制标题
DOI：
10.1016/j.bbamcr.2012.01.014
复制
发表时间：
2012-09
影响因子：
5.1
通讯作者：
Nemeth, Elizabeta
中科院分区：
文献类型：
--
作者：
Ganz, Tomas;Nemeth, Elizabeta
尽管膳食铁摄入量存在波动，并且通过出血间歇性丢失，但人体血浆铁浓度仍稳定在10-30 μM。虽然大部分进入血浆的铁来自回收，但从饮食中吸收适量的铁以补偿损失并在商店中保持无毒量。在实验室啮齿动物中，血浆铁浓度和铁分布也受到类似的调节。肝肽hepcidin被确定为全身性铁调节激素。在传出弧中，铁调素通过诱导其受体（细胞铁输出蛋白ferroportin）的降解来调节肠铁吸收、血浆铁浓度和组织铁分布。膜铁转运蛋白将铁从吸收性肠细胞、回收衰老红细胞铁的巨噬细胞和储存铁的肝细胞输出到血浆中。在更复杂和了解较少的传入弧，肝hepcidin合成转录调控细胞外和细胞内铁浓度通过骨形态发生蛋白受体及其铁特异性配体，调节剂和铁传感器的分子复合物。通过尚未定义的途径，铁调素也通过红细胞前体血红蛋白合成的铁需求进行稳态调节。根据铁调素介导的铁再分布在宿主防御中的作用，铁调素的产生也受到炎症的调节。血浆中铁调素浓度增加在铁限制性贫血中是致病的，包括与炎症、慢性肾病和一些癌症相关的贫血。铁调素缺乏导致遗传性血色素沉着症和无效红细胞生成的铁过载。铁调素、膜铁转运蛋白及其调节剂代表了诊断和治疗铁紊乱和贫血的潜在靶点。
Despite fluctuations in dietary iron intake and intermittent losses through bleeding, the plasma iron concentrations in humans remain stable at 10–30 μM. While most of the iron entering blood plasma comes from recycling, appropriate amount of iron is absorbed from the diet to compensate for losses and maintain nontoxic amounts in stores. Plasma iron concentration and iron distribution are similarly regulated in laboratory rodents. The hepatic peptide hepcidin was identified as the systemic iron-regulatory hormone. In the efferent arc, hepcidin regulates intestinal iron absorption, plasma iron concentrations, and tissue iron distribution by inducing degradation of its receptor, the cellular iron exporter ferroportin. Ferroportin exports iron into plasma from absorptive enterocytes, from macrophages that recycle the iron of senescent erythrocytes, and from hepatocytes that store iron. In the more complex and less well understood afferent arc, hepatic hepcidin synthesis is transcriptionally regulated by extracellular and intracellular iron concentrations through a molecular complex of bone morphogenetic protein receptors and their iron-specific ligands, modulators and iron sensors. Through as yet undefined pathways, hepcidin is also homeostatically regulated by the iron requirements of erythroid precursors for hemoglobin synthesis. In accordance with the role of hepcidin-mediated iron redistribution in host defense, hepcidin production is regulated by inflammation as well. Increased hepcidin concentrations in plasma are pathogenic in iron-restrictive anemias including anemias associated with inflammation, chronic kidney disease and some cancers. Hepcidin deficiency causes iron overload in hereditary hemochromatosis and ineffective erythropoiesis. Hepcidin, ferroportin and their regulators represent potential targets for the diagnosis and treatment of iron disorders and anemias.
登录
查看更多内容
影响因子：
29.4
作者：
Corradini E;Schmidt PJ;Meynard D;Garuti C;Montosi G;Chen S;Vukicevic S;Pietrangelo A;Lin HY;Babitt JL
通讯作者：
Babitt JL
影响因子：
29
作者：
Donovan, A;Lima, CA;Andrews, NC
通讯作者：
Andrews, NC
影响因子：
20.3
作者：
Falzacappa, Maria Vittoria Verga;Spasic, Maja Vujic;Muckenthaler, Martina U.
通讯作者：
Muckenthaler, Martina U.
影响因子：
4
作者：
Hashizume, Misato;Uchiyama, Yasushi;Mihara, Masahiko
通讯作者：
Mihara, Masahiko
影响因子：
20.3
作者：
Ganz, Tomas;Olbina, Gordana;Westerman, Mark
通讯作者：
Westerman, Mark