Astrocyte elevated gene-1 regulates astrocyte responses to neural injury: implications for reactive astrogliosis and neurodegeneration.
Astrocyte elevated gene-1 regulates astrocyte responses to neural injury: implications for reactive astrogliosis and neurodegeneration.
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DOI：
10.1186/1742-2094-9-195
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发表时间：
2012-08-11
影响因子：
9.3
通讯作者：
Ghorpade A
中科院分区：
文献类型：
--
作者：
Vartak-Sharma N;Ghorpade A
反应性星形胶质细胞增生是一种普遍存在但知之甚少的中枢神经系统病理学特征，如创伤和神经退行性疾病。体外和体内研究已经确定了促炎细胞因子和趋化因子作为损伤和疾病期间星形胶质细胞增生的介质;然而，分子机制仍不清楚。在这项研究中，我们确定了星形胶质细胞升高基因-1（AEG-1），一种人类免疫缺陷病毒1型或肿瘤坏死因子α诱导的癌基因，作为反应性星形胶质细胞增生的一种新的调节因子。AEG-1作为侵袭性肿瘤的治疗靶点，在癌症研究领域引起了极大的兴趣。然而，其在星形胶质细胞和星形胶质细胞介导的疾病中的作用知之甚少。基于AEG-1在几种癌症中的致癌作用，我们在此研究AEG-1介导的反应性星形胶质细胞增生过程中星形胶质细胞迁移和增殖的调节。利用体内脑损伤小鼠模型显示反应性星形胶质细胞增生后的AEG-1诱导。进行AEG-1敲低后的体外伤口愈合和细胞迁移测定以分析AEG-1在星形胶质细胞迁移中的作用。AEG-1介导的星形胶质细胞增殖的调节通过使用免疫细胞化学定量细胞增殖标记物Ki 67和增殖细胞核抗原的水平来测定。共聚焦显微镜用于评估AEG-1在损伤后培养的星形胶质细胞中的核仁定位。脑损伤的体内小鼠模型显示出反应性星形胶质细胞与增加的胶质细胞酸性蛋白和AEG-1共定位在伤口部位。在培养的人星形胶质细胞中，AEG-1敲低显著降低了星形胶质细胞向伤口部位的迁移和细胞增殖。共聚焦分析显示AEG-1共定位于损伤的培养人星形胶质细胞的核仁。目前的研究结果首次报道了AEG-1在介导反应性星形胶质细胞增生和调节星形胶质细胞对损伤的反应中的新作用。我们还报道了AEG-1在人星形胶质细胞损伤后的核仁定位。未来的研究可能会致力于阐明AEG-1在星形胶质细胞反应性星形胶质细胞增生过程中的作用的分子机制。
Reactive astrogliosis is a ubiquitous but poorly understood hallmark of central nervous system pathologies such as trauma and neurodegenerative diseases. In vitro and in vivo studies have identified proinflammatory cytokines and chemokines as mediators of astrogliosis during injury and disease; however, the molecular mechanism remains unclear. In this study, we identify astrocyte elevated gene-1 (AEG-1), a human immunodeficiency virus 1 or tumor necrosis factor α-inducible oncogene, as a novel modulator of reactive astrogliosis. AEG-1 has engendered tremendous interest in the field of cancer research as a therapeutic target for aggressive tumors. However, little is known of its role in astrocytes and astrocyte-mediated diseases. Based on its oncogenic role in several cancers, here we investigate the AEG-1-mediated regulation of astrocyte migration and proliferation during reactive astrogliosis. An in vivo brain injury mouse model was utilized to show AEG-1 induction following reactive astrogliosis. In vitro wound healing and cell migration assays following AEG-1 knockdown were performed to analyze the role of AEG-1 in astrocyte migration. AEG-1-mediated regulation of astrocyte proliferation was assayed by quantifying the levels of cell proliferation markers, Ki67 and proliferation cell nuclear antigen, using immunocytochemistry. Confocal microscopy was used to evaluate nucleolar localization of AEG-1 in cultured astrocytes following injury. The in vivo mouse model for brain injury showed reactive astrocytes with increased glial fibrillary acidic protein and AEG-1 colocalization at the wound site. AEG-1 knockdown in cultured human astrocytes significantly reduced astrocyte migration into the wound site and cell proliferation. Confocal analysis showed colocalization of AEG-1 to the nucleolus of injured cultured human astrocytes. The present findings report for the first time the novel role of AEG-1 in mediating reactive astrogliosis and in regulating astrocyte responses to injury. We also report the nucleolar localization of AEG-1 in human astrocytes in response to injury. Future studies may be directed towards elucidating the molecular mechanism of AEG-1 action in astrocytes during reactive astrogliosis.
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影响因子：
15.3
作者：
Brambilla, R;Bracchi-Ricard, V;Hu, WH;Frydel, B;Bramwell, A;Karmally, S;Green, EJ;Bethea, JR
通讯作者：
Bethea, JR
DOI：
10.1083/jcb.201105143
发表时间：
2011-09-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Boyd MT;Vlatkovic N;Rubbi CP
通讯作者：
Rubbi CP
影响因子：
1.2
作者：
Jeon, Hyun Yong;Choi, Murim;Fisher, Paul B.
通讯作者：
Fisher, Paul B.
影响因子：
3.5
作者：
Aschner, M
通讯作者：
Aschner, M
影响因子：
5.3
作者：
Daginakatte, Girish C.;Gadzinski, Adam;Gutmann, David H.
通讯作者：
Gutmann, David H.