Hepcidin inhibits in vitro erythroid colony formation at reduced erythropoietin concentrations
Hepcidin inhibits in vitro erythroid colony formation at reduced erythropoietin concentrations
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DOI：
10.1182/blood-2005-07-2854
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发表时间：
2006-04-01
期刊：
影响因子：
20.3
通讯作者：
Means, RT
中科院分区：
文献类型：
--
作者：
Dallalio, G;Law, E;Means, RT
慢性病性贫血（ACD）由3个主要过程引起：红细胞存活期轻微缩短、网状内皮系统铁动员受损和红细胞生成受损。铁调素是一种具有特异性铁调节特性的急性期蛋白，其沿着铁调素表达增加所见的贫血，已导致许多人认为其是ACD的主要介质。然而，如果铁调素是导致ACD的主要因素，那么它也应该有助于在该综合征中观察到的红细胞生成受损。在红细胞生成素（Epo）浓度小于或等于0.5 U/mL时，铁调素抑制体外红细胞集落形成，但在Epo 1.0 U/mL时不抑制。在Epo浓度为0.3 U/mL时，与对照组相比，暴露于铁调素的HCD 57红白血病细胞表现出抗凋亡蛋白pBad的表达降低。这些研究表明，铁调素可能不仅通过影响铁代谢，而且通过抑制红系祖细胞增殖和存活而导致ACID贫血。
The anemia of chronic disease (ACD) results from 3 major processes: slightly shortened red cell survival, impaired reticuloendothelial system iron mobilization, and impaired erythropoiesis. Hepcidin is an acute-phase protein with specific iron regulatory properties, which, along with the anemia seen with increased hepcidin expression, have led many to consider it the major mediator of ACD. However, if hepcidin is the major factor responsible for ACD, then it should also contribute to the impaired erythropoiesis observed in this syndrome. Erythroid colony formation in vitro was inhibited by hepcidin at erythropoietin (Epo) concentrations less than or equal to 0.5 U/mL but not at Epo 1.0 U/mL. At Epo concentrations of 0.3 U/mL, HCD57 erythroleukemia cells exposed to hepcidin exhibit decreased expression of the antiapoptotic protein pBad compared with controls. These studies suggest that hepcidin may contribute to anemia in ACID not only through effects on iron metabolism, but also through inhibition of erythroid progenitor proliferation and survival.