Astrocytic CCAAT/Enhancer-Binding Protein Delta Contributes to Glial Scar Formation and Impairs Functional Recovery After Spinal Cord Injury

Shao Ming Wang, Jung-Yu Hsu, Chiung Yuan Ko, Nai En Chiu, Wai-Ming Kan, Ming-Derg Lai, Ju-Ming Wang

研究成果: Article

4 引文 (Scopus)

摘要

After spinal cord injury, inflammatory reaction induces the aggregation of astrocytes to form a glial scar that eventually blocks axonal regeneration. Transcription factor CCAAT/enhancer-binding protein delta (C/EBPδ) is a regulatory protein of genes responsive to inflammatory factors, but its role in glial scar formation after spinal cord injury remains unknown. By using a model of moderate spinal cord contusion injury at the mid-thoracic level, we found that C/EBPδ was expressed mostly in the reactive astrocytes bordering the lesion in wild-type mice from 7 days after the injury. C/EBPδ-deficient mice showed reduced glial scar formation, more residual white matter, and better motor function recovery compared with wild-type mice 28 days after the injury. Upon interleukin (IL)-1β stimulation in vitro, the increased expression of C/EBPδ in reactive astrocytes inhibited RhoA expression and, subsequently, the ability of astrocyte migration. However, these reactive astrocytes also produced an increased amount of matrix metalloproteinase-3, which promoted the migration of non-IL-1β-treated, inactive astrocytes. Although the involvement of other non-astroglial C/EBPδ cannot be entirely excluded, our studies suggest that astrocytic C/EBPδ is integral to the inflammatory cascades leading to glial scar formation after spinal cord injury.

原文English
頁(從 - 到)5912-5927
頁數16
期刊Molecular Neurobiology
53
發行號9
DOIs
出版狀態Published - 2016 十一月 1

指紋

CCAAT-Enhancer-Binding Protein-delta
Spinal Cord Injuries
Neuroglia
Astrocytes
Cicatrix
Matrix Metalloproteinase 3
Recovery of Function
Wounds and Injuries
Regulator Genes
Interleukin-1
Regeneration
Transcription Factors
Thorax

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

引用此文

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abstract = "After spinal cord injury, inflammatory reaction induces the aggregation of astrocytes to form a glial scar that eventually blocks axonal regeneration. Transcription factor CCAAT/enhancer-binding protein delta (C/EBPδ) is a regulatory protein of genes responsive to inflammatory factors, but its role in glial scar formation after spinal cord injury remains unknown. By using a model of moderate spinal cord contusion injury at the mid-thoracic level, we found that C/EBPδ was expressed mostly in the reactive astrocytes bordering the lesion in wild-type mice from 7 days after the injury. C/EBPδ-deficient mice showed reduced glial scar formation, more residual white matter, and better motor function recovery compared with wild-type mice 28 days after the injury. Upon interleukin (IL)-1β stimulation in vitro, the increased expression of C/EBPδ in reactive astrocytes inhibited RhoA expression and, subsequently, the ability of astrocyte migration. However, these reactive astrocytes also produced an increased amount of matrix metalloproteinase-3, which promoted the migration of non-IL-1β-treated, inactive astrocytes. Although the involvement of other non-astroglial C/EBPδ cannot be entirely excluded, our studies suggest that astrocytic C/EBPδ is integral to the inflammatory cascades leading to glial scar formation after spinal cord injury.",
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AU - Chiu, Nai En

AU - Kan, Wai-Ming

AU - Lai, Ming-Derg

AU - Wang, Ju-Ming

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