p75NTR Promotes Astrocyte Proliferation in Response to Cortical Stab Wound
p75NTR Promotes Astrocyte Proliferation in Response to Cortical Stab Wound
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p75NTR 促进星形胶质细胞增殖以应对皮质刺伤
DOI：
10.1007/s10571-020-01006-x
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发表时间：
2020-11-17
影响因子：
4
通讯作者：
Liao, Hong
中科院分区：
文献类型：
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作者：
Chen, Mingming;Guo, Linlu;Liao, Hong
脑外伤后的星形胶质细胞增生对功能恢复有显著影响。然而，对星形胶质细胞增殖和随后的星形胶质细胞增生的机制知之甚少。在这项研究中，我们建立了一个皮质刺伤损伤小鼠模型，并观察到戏剧性的星形胶质细胞激活和神经生长因子受体（p75 NTR）上调附近的病变。我们还发现病变附近星形胶质细胞的细胞周期发生了深刻的变化，从有丝分裂静止（G 0）期到G2/M和S期的转变。然而，没有观察到星形胶质细胞凋亡水平的变化。在小鼠星形胶质细胞中p75 NTR敲低后，细胞周期进展到G2/M和S期以及响应皮质刺伤的CDK 2蛋白水平被抑制。相反，小鼠星形胶质细胞中p75 NTR过表达足以促进细胞周期进展。总之，我们的研究结果表明，脑损伤后星形胶质细胞中p75 NTR上调通过促进CDK 2表达和促进星形胶质细胞增殖诱导细胞周期进入。我们的研究结果提供了一个更好的理解星形胶质细胞的反应后，皮质刺伤损伤小鼠。
Astrogliosis after brain trauma can have a significant impact on functional recovery. However, little is known about the mechanisms underlying astrocyte proliferation and subsequent astrogliosis. In this study, we established a cortical stab wound injury mouse model and observed dramatic astrocyte activation and nerve growth factor receptor (p75NTR) upregulation near the lesion. We also found profound alterations in the cell cycle of astrocytes near the lesion, with a switch from a mitotically quiescent (G0) phase to the G2/M and S phases. However, no changes in the level of astrocyte apoptosis were observed. Cell cycle progression to the G2/M and S phases and CDK2 protein levels in response to cortical stab wound was inhibited after p75NTR knockdown in mouse astrocytes. Conversely, p75NTR overexpression in mouse astrocytes was sufficient in promoting cell cycle progression. In conclusion, our results suggested that p75NTR upregulation in astrocytes after brain injury induces cell cycle entry by promoting CDK2 expression and promoting astrocyte proliferation. Our findings provided a better understanding of astrocytic responses after cortical stab wound injury in mice.