Erythropoietin promotes regeneration of adult CNS neurons via Jak2/Stat3 and PI3K/Akt pathway activation
Erythropoietin promotes regeneration of adult CNS neurons via Jak2/Stat3 and PI3K/Akt pathway activation
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DOI：
10.1016/j.mcn.2005.04.009
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发表时间：
2005-08-01
影响因子：
3.5
通讯作者：
Isenmann, S
中科院分区：
文献类型：
--
作者：
Kretz, A;Happold, CJ;Isenmann, S
细胞因子激素促红细胞生成素（EPO）已被证明在中枢神经系统损伤中具有神经保护作用，用于缺血性卒中的临床试验正在进行中。EPO通过纤维再生恢复有丝分裂后CNS结构和功能的能力尚未被研究。在这里，我们比较了体外生长能力的成年视网膜神经节细胞（RGC）视神经（ON）损伤的存在和不存在的EPO。在体内立即EPO调节，或用10- 10，000 IU rhEPO延迟EPO处理培养物显著增加新产生的神经突的数量（2.66倍）和长度（8.31倍），而不引起流变学并发症。EPO诱导RGC中Stat 3磷酸化，抑制Jak 2/Stat 3可消除EPO诱导的生长。EPO促进的轴突发生被Bcl-X-L（一种能够促进RGC再生的BcI-2同源物）的上调所抑制。PI 3 K/Akt途径也可能参与抗细胞凋亡和增强再生的EPO作用。总之，EPO治疗可能提供一种独特的神经保护和再生的双重功能策略。(c)2005年爱思唯尔公司All rights reserved.
The cytokine hormone erythropoietin (EPO) has proved neuroproteetive in CNS injury, and clinical trials for ischemic stroke are ongoing. The capability of EPO to restore postmitotic CNS architecture and function by fibre regeneration has not been examined. Here, we compared in vitro outgrowth capacity of adult retinal ganglion cells (RGCs) following optic nerve (ON) lesion in the presence and absence of EPO. Immediate EPO conditioning in vivo, or delayed EPO treatment of cultures with 10-10,000 IU rhEPO significantly increased numbers (2.66-fold) and length (8.31-fold) of newly generated neurites, without evoking rheological complications. EPO induced Stat3 phosphorylation in RGCs, and inhibition of Jak2/Stat3 abolished EPO-induced growth. EPO-facilitated neuritogenesis was paralleled by upregulation of Bcl-X-L, a BcI-2 homologue capable of promoting RGC regeneration. The PI3K/Akt pathmay was also involved in antiapoptotic and regeneration-enhancing EPO actions. In conclusion, EPO treatment may offer a unique dual-function strategy for neuroprotection and regeneration. (c) 2005 Elsevier Inc. All rights reserved.