Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBPalpha.
Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBPalpha.
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DOI：
10.1182/blood-2007-08-106195
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发表时间：
2008-06-15
期刊：
影响因子：
20.3
通讯作者：
Porto G
中科院分区：
文献类型：
--
作者：
Pinto JP;Ribeiro S;Pontes H;Thowfeequ S;Tosh D;Carvalho F;Porto G
铁调素是主要的铁调节激素，控制全身吸收和从细胞内储存的铁的再动员。最近的体内研究表明，铁调素是下调红细胞生成，贫血，缺氧，这满足了铁输入红细胞生产的需要。促红细胞生成素（EPO）是在贫血和缺氧条件下触发红细胞生成的主要信号。因此，可以假设EPO直接参与铁调素调节。我们在这里报告的铁调素表达的EPO的调节，以剂量依赖性的方式，在新鲜分离的小鼠肝细胞和HepG 2人肝细胞模型。该作用通过EPOR信号传导介导，因为铁调素mRNA水平通过用EPOR阻断抗体预处理而恢复。在EPO和抗EPOR处理后，转录因子C/EBPα在mRNA和蛋白水平上显示出与hepcidin相似的表达模式。染色质免疫沉淀实验显示，EPO补充后，C/EBPα与铁调素启动子的结合显著减少，表明该转录因子参与了铁调素对EPO的转录应答。
Hepcidin is the principal iron regulatory hormone, controlling the systemic absorption and remobilization of iron from intracellular stores. Recent in vivo studies have shown that hepcidin is down-regulated by erythropoiesis, anemia, and hypoxia, which meets the need of iron input for erythrocyte production. Erythropoietin (EPO) is the primary signal that triggers erythropoiesis in anemic and hypoxic conditions. Therefore, a direct involvement of EPO in hepcidin regulation can be hypothesized. We report here the regulation of hepcidin expression by EPO, in a dose-dependent manner, in freshly isolated mouse hepatocytes and in the HepG2 human hepatocyte cell model. The effect is mediated through EPOR signaling, since hepcidin mRNA levels are restored by pretreatment with an EPOR-blocking antibody. The transcription factor C/EBPα showed a pattern of expression similar to hepcidin, at the mRNA and protein levels, following EPO and anti-EPOR treatments. Chromatin immunoprecipitation experiments showed a significant decrease of C/EBPα binding to the hepcidin promoter after EPO supplementation, suggesting the involvement of this transcription factor in the transcriptional response of hepcidin to EPO.
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影响因子：
10.5
作者：
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影响因子：
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Carvalho, M;Carvalho, F;Bastos, ML
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DOI：
10.1016/j.biocel.2007.05.015
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