Endogenous Erythropoietin From Astrocyte Protects the Oligodendrocyte Precursor Cell Against Hypoxic and Reoxygenation Injury
Endogenous Erythropoietin From Astrocyte Protects the Oligodendrocyte Precursor Cell Against Hypoxic and Reoxygenation Injury
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DOI：
10.1002/jnr.22702
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发表时间：
2011-10-01
影响因子：
4.2
通讯作者：
Asai, Kiyofumi
中科院分区：
文献类型：
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作者：
Kato, Shin;Aoyama, Mineyoshi;Asai, Kiyofumi
缺氧反应性细胞因子促红细胞生成素（EPO）在缺血事件和神经退行性疾病期间在受损的脑中提供神经保护作用。本研究旨在探讨缺氧条件下星形胶质细胞与少突胶质细胞前体细胞（OPC）之间EPO/EPO受体（EPOR）的内源性系统。我们在这里报告升高EPO mRNA水平和蛋白质释放培养星形胶质细胞缺氧刺激后，通过定量RT-PCR和ELISA。定量RT-PCR检测星形胶质细胞和小胶质细胞中EPOR基因的表达。细胞染色显示OPC中EPOR的表达。为了评价内源性EPO对星形胶质细胞向OPCs的保护作用，在体外研究中，通过EPO siRNA或EPOR siRNA基因沉默来阻断EPO/EPOR信号传导。EPO siRNA抑制星形胶质细胞内源性EPO的产生，降低了OPCs对缺氧应激的保护作用。此外，OPC-EPOR siRNA在缺氧/复氧损伤后的细胞存活率较低。提示缺氧/复氧条件下，星形胶质细胞向OPC的EPO/EPOR信号通路可防止OPC损伤。我们目前发现的星形胶质细胞和OPCs之间的相互作用可能导致一个新的治疗方法OPCs用于对抗细胞应激和损伤。(C)2011 Wiley-Liss，Inc.
The hypoxia-responsive cytokine erythropoietin (EPO) provides neuroprotective effects in the damaged brain during ischennic events and neurodegenerative diseases. The purpose of the present study is to evaluate the EPO/EPO receptor (EPOR) endogenous system between astrocyte and oligodendrocyte precursor cell (OPC) under hypoxia. We report here elevated EPO mRNA levels and protein release in cultured astrocytes following hypoxic stimulation by quantitative RT-PCR and ELISA. Furthermore, the EPOR gene expressions were detected in cultured OPCs as in astrocytes and microglias by quantitative RT-PCR. Cell staining revealed the EPOR expression in OPC. To evaluate the protective effect of endogenous EPO from astrocyte to OPCs, EPO/EPOR signaling was blocked by EPO siRNA or EPOR siRNA gene silencing in in vitro study. The suppression of endogenous EPO production in astrocytes by EPO siRNA decreased the protection to OPCs against hypoxic stress. Furthermore, OPC with EPOR siRNA had less cell survival after hypoxic/reoxygenation injury. This suggested that EPO/EPOR signaling from astrocyte to OPC could prevent OPC damage under hypoxic/reoxygenation condition. Our present finding of an interaction between astrocytes and OPCs may lead to a new therapeutic approach to OPCs for use against cellular stress and injury. (C) 2011 Wiley-Liss, Inc.