Astrocyte elevated gene-1 regulates astrocyte responses to neural injury: implications for reactive astrogliosis and neurodegeneration
<p>Abstract</p> <p>Background</p> <p>Reactive astrogliosis is a ubiquitous but poorly understood hallmark of central nervous system pathologies such as trauma and neurodegenerative diseases. <it>In vitro</it> and <it>in vivo</it> studies have ide...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-08-01
|
| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://www.jneuroinflammation.com/content/9/1/195 |
| _version_ | 1818360283031142400 |
|---|---|
| author | Vartak-Sharma Neha Ghorpade Anuja |
| author_facet | Vartak-Sharma Neha Ghorpade Anuja |
| author_sort | Vartak-Sharma Neha |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Reactive astrogliosis is a ubiquitous but poorly understood hallmark of central nervous system pathologies such as trauma and neurodegenerative diseases. <it>In vitro</it> and <it>in vivo</it> 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.</p> <p>Methods</p> <p>An <it>in vivo</it> brain injury mouse model was utilized to show AEG-1 induction following reactive astrogliosis. <it>In vitro</it> 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.</p> <p>Results</p> <p>The <it>in vivo</it> 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.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-13T20:58:19Z |
| format | Article |
| id | doaj.art-6102a00ff65f4f1d87271f9f6174f9f5 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-13T20:58:19Z |
| publishDate | 2012-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-6102a00ff65f4f1d87271f9f6174f9f52022-12-21T23:31:41ZengBMCJournal of Neuroinflammation1742-20942012-08-019119510.1186/1742-2094-9-195Astrocyte elevated gene-1 regulates astrocyte responses to neural injury: implications for reactive astrogliosis and neurodegenerationVartak-Sharma NehaGhorpade Anuja<p>Abstract</p> <p>Background</p> <p>Reactive astrogliosis is a ubiquitous but poorly understood hallmark of central nervous system pathologies such as trauma and neurodegenerative diseases. <it>In vitro</it> and <it>in vivo</it> 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.</p> <p>Methods</p> <p>An <it>in vivo</it> brain injury mouse model was utilized to show AEG-1 induction following reactive astrogliosis. <it>In vitro</it> 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.</p> <p>Results</p> <p>The <it>in vivo</it> 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.</p> <p>Conclusions</p> <p>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.</p>http://www.jneuroinflammation.com/content/9/1/195AEG-1AstrocyteHIV-1Reactive astrogliosis |
| spellingShingle | Vartak-Sharma Neha Ghorpade Anuja Astrocyte elevated gene-1 regulates astrocyte responses to neural injury: implications for reactive astrogliosis and neurodegeneration Journal of Neuroinflammation AEG-1 Astrocyte HIV-1 Reactive astrogliosis |
| title | Astrocyte elevated gene-1 regulates astrocyte responses to neural injury: implications for reactive astrogliosis and neurodegeneration |
| title_full | Astrocyte elevated gene-1 regulates astrocyte responses to neural injury: implications for reactive astrogliosis and neurodegeneration |
| title_fullStr | Astrocyte elevated gene-1 regulates astrocyte responses to neural injury: implications for reactive astrogliosis and neurodegeneration |
| title_full_unstemmed | Astrocyte elevated gene-1 regulates astrocyte responses to neural injury: implications for reactive astrogliosis and neurodegeneration |
| title_short | Astrocyte elevated gene-1 regulates astrocyte responses to neural injury: implications for reactive astrogliosis and neurodegeneration |
| title_sort | astrocyte elevated gene 1 regulates astrocyte responses to neural injury implications for reactive astrogliosis and neurodegeneration |
| topic | AEG-1 Astrocyte HIV-1 Reactive astrogliosis |
| url | http://www.jneuroinflammation.com/content/9/1/195 |
| work_keys_str_mv | AT vartaksharmaneha astrocyteelevatedgene1regulatesastrocyteresponsestoneuralinjuryimplicationsforreactiveastrogliosisandneurodegeneration AT ghorpadeanuja astrocyteelevatedgene1regulatesastrocyteresponsestoneuralinjuryimplicationsforreactiveastrogliosisandneurodegeneration |