Decreased DMT1 and increased ferroportin 1 expression is the mechanisms of reduced iron retention in macrophages by erythropoietin in rats
Decreased DMT1 and increased ferroportin 1 expression is the mechanisms of reduced iron retention in macrophages by erythropoietin in rats
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DOI：
10.1002/jcb.21654
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发表时间：
2008-05-15
影响因子：
4
通讯作者：
Chang, Yan-Zhong
中科院分区：
文献类型：
--
作者：
Kong, Wei-Na;Zhao, Shu-E;Chang, Yan-Zhong
从网状内皮巨噬细胞到红系前体细胞的再循环铁对于维持铁稳态很重要。然而，人们对巨噬细胞铁稳态的分子机制知之甚少。在这项研究中，雄性 Sprague-Dawley 大鼠接受重组人促红细胞生成素（rHuEpo，500 IU/天，皮下注射）治疗 3 天。第5天，收获腹腔渗出液巨噬细胞，采用液体闪烁计数法测定Fe-55的摄取和释放。 RT-PCR和Western blot检测腹膜I型渗出液巨噬细胞中二价金属转运蛋白1（DMTI）和铁转运蛋白]（FPN 1）的表达。为了排除rHuEpo对巨噬细胞的直接影响，用rHuEpo (2 IU/ml)孵育正常腹膜渗出液巨噬细胞进行平行实验。我们的结果显示 rHuEpo 注射减少了腹膜渗出物巨噬细胞的铁保留。 Fe(II) 的摄取通过抑制 DMT] (+IRE) 表达而减少，而 Fe(II)) 的释放则随着巨噬细胞中 FPN 1 表达的增加而增加。此外，rHuEpo处理的大鼠肝脏中HAMP mRNA的表达比对照组(CG)低四倍。 HAMP mRNA 表达增加；体外rHuEpo处理后正常腹腔渗出巨噬细胞DMT1合成无明显变化，而FPN1减少。我们得出结论，铁调素可能在 FPN1 合成的变化中发挥重要的致病作用，并减少 rHuEpo 处理的大鼠巨噬细胞中铁的保留。
Recycled iron from reticuloendothelial macrophages to erythroid precursors is important to maintain the iron homeostasis. However, the molecular mechanisms underlying iron homeostasis in macrophages are poorly understood. In this study, male Sprague-Dawley rats were treated with recombinant human erythropoietin (rHuEpo, 500 IU/day, s.c.) for 3 days. At the fifth day, peritoneal exudate macrophages were harvested, and then Fe-55 uptake and release were measured by liquid scintillation counting method. The expression of divalent metal transporter 1 (DMTI)and ferroportin] (FPN 1) in peritonea I exudate macrophages was detected by RT-PCR and Western blot. In order to exclude the direct effect of rHuEpo on macrophages, the parallel experiments were performed with incubation normal peritoneal exudate macrophages with rHuEpo (2 IU/ml). Our results showed rHuEpo injection reduced the peritoneal exudate macrophages iron retention. The uptake of Fe(II) was decreased via the suppression of DMT] (+IRE) expression and the release of Fe(II)) was increased with increasing the expression of FPN 1 in macrophages. Moreover, the express ion of HAMP mRNA was four times lower in rHuEpo-treated liver of rats than control group (CG). HAMP mRNA expression was increased; the synthesis of DMT1 had no significant change, whereas the FPN1 was decreased in normal peritoneal exudate macrophages after treatment with rHuEpo in vitro. We conclude that hepcidin may play a major, causative role in the change of FPN1 synthesis and that decreased the iron retention in macrophages of rHuEpo-treated rats.