The Expression of NP847 and Sox2 after TBI and Its Influence on NSCs.

The Expression of NP847 and Sox2 after TBI and Its Influence on NSCs.
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TBI后NP847和Sox2的表达及其对NSCs的影响。

DOI:
10.3389/fncel.2016.00282
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发表时间:
2016
影响因子:
5.3
通讯作者:
Shi W
Shi W
中科院分区:
医学2区
文献类型:
--
作者:
Gu J;Bao Y;Chen J;Huang C;Zhang X;Jiang R;Liu Q;Liu Y;Xu X;Shi W

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神经干细胞的增殖和分化对脑损伤后的神经再生具有重要作用。在这里,我们第一次证明,磷酸化(P)-ser847-nNOS(NP847),而不是nNOS,可能在创伤性脑损伤(TBI)后NSC的增殖中起主要作用。Western印迹结果显示,颅脑损伤后海马区NP847和Sox2的表达上调,并在伤后3天达到高峰。此外,免疫荧光实验表明,NP847和SOX2部分共定位于脑损伤后神经干细胞的细胞核中。进一步的免疫沉淀实验发现,NP847和Sox2在神经干细胞中可以直接相互作用。此外,在NSCs的OGD模型中,NP847的表达降低,随后Sox2的表达下调。有趣的是,在本研究中,我们没有观察到OGD模型中nNOS表达的变化。进一步的研究数据表明,NP847-Sox2复合体可能在脑损伤后通过Shh/Gli信号通路以CaMKII依赖的方式在NSCs中发挥重要作用。
The proliferation and differentiation of neural stem cells (NSCs) is important for neural regeneration after cerebral injury. Here, for the first time, we show that phosphorylated (p)-ser847-nNOS (NP847), rather than nNOS, may play a major role in NSC proliferation after traumatic brain injury (TBI). Western blot results demonstrated that the expression of NP847 and Sox2 in the hippocampus is up-regulated after TBI, and they both peak 3 days after brain injury. In addition, an immunofluorescence experiment indicated that NP847 and Sox2 partly co-localize in the nuclei of NSCs after TBI. Further immunoprecipitation experiments found that NP847 and Sox2 can directly interact with each other in NSCs. Moreover, in an OGD model of NSCs, NP847 expression is decreased, which is followed by the down-regulation of Sox2. Interestingly, in this study, we did not observe changes in the expression of nNOS in the OGD model. Further research data suggest that the NP847-Sox2 complex may play a major role in NSCs through the Shh/Gli signaling pathway in a CaMKII-dependent manner after brain injury.
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