[1]陈星星,王冠,刘明永,等.Sox2在NT-3促进大鼠神经干细胞分化中的作用[J].第三军医大学学报,2015,37(04):304-309.
 Chen Xingxing,Wang Guan,Liu Mingyong,et al.Effect of Sox2 on NT-3-induced differentiation in rat neural stem cells[J].J Third Mil Med Univ,2015,37(04):304-309.
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Sox2在NT-3促进大鼠神经干细胞分化中的作用(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
37卷
期数:
2015年第04期
页码:
304-309
栏目:
论著
出版日期:
2015-02-28

文章信息/Info

Title:
Effect of Sox2 on NT-3-induced differentiation in rat neural stem cells
作者:
陈星星王冠刘明永薛鑫郭乔楠赵建华
第三军医大学大坪医院野战外科研究所脊柱外科;第三军医大学新桥医院病理科
Author(s):
Chen Xingxing Wang Guan Liu Mingyong Xue Xin Guo Qiaonan Zhao Jianhua

Department of Spine Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042;Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China

关键词:
NT-3Sox2神经干细胞分化PI3K/AKT信号通路
Keywords:
NT-3 Sox2 neural stem cells differentiation PI3K/AKT signal pathway
分类号:
R322.81;R329.21;R329.26
文献标志码:
A
摘要:

目的      探讨Sox2在神经营养因子3(neurotrophin-3,NT-3)促进原代大鼠神经干细胞(neural stem cells,NSCs)分化中的作用及其机制。      方法      选取孕14~15 d SD胎鼠,培养原代脑源性NSCs。观察NT-3对NSCs中Sox2表达及NSCs分化的影响:采用不同浓度NT-3(25、50、100 ng/mL)刺激NSCs24 h后,检测Sox2、DCX、Olig2、GFAP蛋白的表达量。探索NT-3对Sox2产生影响的机制:使用PI3K/AKT通路阻断剂(10 μmol/L LY294002)选择性阻断NT-3的作用后,检测AKT、p-AKT和Sox2在蛋白水平表达量的变化。      结果      随着NT-3浓度的升高,NSCs中Sox2蛋白水平的表达明显上调(P<0.05),各NT-3处理组的NSCs向神经元前体细胞分化的比例明显增加(P<0.05),100 ng/mL NT-3组效果最强,呈现出明显的剂量依赖性;与对照组相比,100 ng/mL NT-3组的p-AKT及Sox2蛋白水平显著上调(P<0.05),且LY294002可阻断此作用(P<0.05)。      结论      NT-3能够上调NSCs中Sox2的表达,后者进而诱导NSCs向神经元方向分化,其可能是通过激活PI3K/AKT信号通路起作用。

Abstract:

Objective      To investigate the effect of SRY (sex determining region Y)-box 2 (Sox2) on neutrotrophin-3 (NT-3)-induced differentiation of rat brain-derived neural stem cells (NSCs).       Methods      NSCs were isolated from Sprague-Dawley (SD) rat embryos (14-15 d) and cultured in vitro. Then, NSCs were randomized into control group, 25 ng/mL NT-3 group, 50 ng/mL NT-3 group, and 100 ng/mL NT-3 group. After the cells in all the groups were cultured for 24 h, the expressions of Sox2, doublecortin (DCX), oligodendrocyte transcription factor 2 (Olig2), and glial fibrillary acidic protein (GFAP) were assessed by Western blotting and immunofluorescence assay. Besides, NSCs were randomized into control group, 10 μmol/L PI3K/AKT pathway inhibitor (LY294002) group, 100 ng/mL NT-3 group, and LY294002 (10 μmol/L)+NT-3 (100 ng/mL) group. After the cells were cultured for 24 h, the expressions of AKT, p-AKT and Sox2 proteins were detected.       Results      The Sox2 protein expression was significantly up-regulated along with the concentration increase of NT-3 (P<0.05), and the proportion of neuronal precursor cells differentiated from the NSCs was increased in a dose-dependent manner (P<0.05). The 100 ng/mL NT-3 group markedly up-regulated the expression of p-AKT and Sox2 proteins as compared with the control group (P<0.05), and the up-regulation could be blocked with LY294002 (P<0.05).       Conclusion      Sox2 induces the differentiation of NSCs to neuronal precursor cells, and NT-3 up-regulates the Sox2 expression through activating PI3K/AKT signal pathway.

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更新日期/Last Update: 2015-01-30