Erythropoietin promotes axonal regeneration after optic nerve crush in vivo by inhibition of RhoA/ROCK signaling pathway
Erythropoietin promotes axonal regeneration after optic nerve crush in vivo by inhibition of RhoA/ROCK signaling pathway
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DOI：
10.1016/j.neuropharm.2012.06.037
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发表时间：
2012-11
影响因子：
4.7
通讯作者：
Haibo Tan;Y. Zhong;Xi Shen;Y. Cheng;Qin Jiao;L. Deng
中科院分区：
文献类型：
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作者：
Haibo Tan;Y. Zhong;Xi Shen;Y. Cheng;Qin Jiao;L. Deng
我们研究了RhoA/ROCK通路是否参与促红细胞生成素（EPO）促进大鼠视神经挤压（ONC）模型中视网膜神经节细胞（RGCs）轴突再生的作用。我们证明，EPO和ROCK抑制剂Y-27632在体内显著增强RGCs存活和轴突再生，并且这些药剂的作用是相加的。EPO或Y-27632经pull down试验和亲和沉淀后，活性RhoA的表达降低。根据免疫组织化学和蛋白质印迹分析，EPO和Y-27632混合物的施用导致甚至更多的RhoA失活，ROCK-1和ROCK-2的表达降低，以及生长相关蛋白-43（GAP-43）蛋白的表达增加。EPO下调活性RhoA、ROCK-1和ROCK-2表达与大量再生轴突的出现一致。结论：RhoA/ROCK信号通路参与EPO促进ONC后RGCs轴突再生的作用。
We investigated whether the RhoA/ROCK pathway was involved in the effect of erythropoietin (EPO) to promote retinal ganglion cells (RGCs) axonal regeneration in a rat optic nerve crush (ONC) model. We demonstrated that both EPO and ROCK inhibitor Y-27632 significantly enhanced RGCs survival and axon regeneration in vivo, and the effects of these agents were additive. Expression of active-RhoA was decreased after EPO or Y-27632 per pull down assay and affinity precipitation. Administration of EPO and Y-27632 cocktail resulted in even more RhoA inactivation, decreased expression of ROCK-1 and ROCK-2, and increased expression of growth associated protein-43 (GAP-43) protein per immunohistochemistry and western blot analysis. Down-regulation of active-RhoA, ROCK-1, and ROCK-2 expression by EPO coincided with the appearance of larger numbers of regenerating axons. In conclusion, the RhoA/ROCK signaling pathway was involved in the EPO effect to promote RGCs axon regeneration after ONC.