Shi Yulong, Yi Chengla, Li Xiao, Wang Jiangpeng, Zhou Fangyuan, Chen Xiaoqian
Department of Traumatic Surgery, Tong-ji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Jie Fang Avenue 1095, China.
Department of Traumatic Surgery, Tong-ji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Jie Fang Avenue 1095, China.
Neurosci Lett. 2017 Feb 3;639:68-73. doi: 10.1016/j.neulet.2016.12.052. Epub 2016 Dec 22.
Glia scar is a hallmark in late-stage of brain stroke disease, which hinder axonal regeneration and neuronal repair. Mitofusin2 (Mfn2) is a newly found cellular proliferation inhibitor. This study is to elucidate the role of Mfn2 in reactive astrocytes induced by oxygen-glucose deprivation/reoxygenation(OGD/R) model in vitro. Up-expression in EdU staining and protein level of GFAP, PCNA and CyclinD1, demonstrates the distinct activation and proliferation of astrocytes after the stimulation of OGD/R. Meanwhile, Mfn2 was proved to be down-regulated both in gene and protein levels. Pretreatment of cells with adenoviral vector encoding Mfn2 gene increased Mfn2 expression and subsequently attenuated OGD-induced astrocyte proliferation. Down-regulation of Ras-p-Raf1-p-ERK1/2 pathway and cell cycle arrest were found to be relevant. Together, these results suggested that overexpression of Mfn2 can effectively inhibit the proliferation of reactive astrogliosis, which might contribute to a promising therapeutic intervention in cerebral ischemic injury.
胶质瘢痕是脑卒中疾病晚期的一个标志,它会阻碍轴突再生和神经元修复。线粒体融合蛋白2(Mfn2)是一种新发现的细胞增殖抑制剂。本研究旨在阐明Mfn2在体外氧糖剥夺/复氧(OGD/R)模型诱导的反应性星形胶质细胞中的作用。EdU染色以及GFAP、PCNA和CyclinD1蛋白水平的上调,表明在OGD/R刺激后星形胶质细胞有明显的激活和增殖。同时,Mfn2在基因和蛋白水平均被证明下调。用编码Mfn2基因的腺病毒载体预处理细胞可增加Mfn2表达,随后减弱OGD诱导的星形胶质细胞增殖。发现Ras-p-Raf1-p-ERK1/2信号通路的下调和细胞周期阻滞与之相关。总之,这些结果表明Mfn2的过表达可以有效抑制反应性星形胶质细胞增生,这可能为脑缺血损伤提供一种有前景的治疗干预手段。