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

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5912-5927
JournalMolecular Neurobiology
Volume53
Issue number9
DOIs
Publication statusPublished - Nov 1 2016

Fingerprint

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

Keywords

  • Astrocyte migration
  • Astrogliosis
  • C/EBPδ
  • MMP-3
  • RhoA

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Astrocytic CCAAT/Enhancer-Binding Protein Delta Contributes to Glial Scar Formation and Impairs Functional Recovery After Spinal Cord Injury. / Wang, Shao Ming; Hsu, Jung Yu C; Ko, Chiung Yuan; Chiu, Nai En; Kan, Wai Ming; Lai, Ming Derg; Wang, Ju Ming.

In: Molecular Neurobiology, Vol. 53, No. 9, 01.11.2016, p. 5912-5927.

Research output: Contribution to journalArticle

Wang, Shao Ming ; Hsu, Jung Yu C ; Ko, Chiung Yuan ; Chiu, Nai En ; Kan, Wai Ming ; Lai, Ming Derg ; Wang, Ju Ming. / Astrocytic CCAAT/Enhancer-Binding Protein Delta Contributes to Glial Scar Formation and Impairs Functional Recovery After Spinal Cord Injury. In: Molecular Neurobiology. 2016 ; Vol. 53, No. 9. pp. 5912-5927.
@article{f537a53b7ff1424fa1af02503a48f69c,
title = "Astrocytic CCAAT/Enhancer-Binding Protein Delta Contributes to Glial Scar Formation and Impairs Functional Recovery After Spinal Cord Injury",
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.",
keywords = "Astrocyte migration, Astrogliosis, C/EBPδ, MMP-3, RhoA",
author = "Wang, {Shao Ming} and Hsu, {Jung Yu C} and Ko, {Chiung Yuan} and Chiu, {Nai En} and Kan, {Wai Ming} and Lai, {Ming Derg} and Wang, {Ju Ming}",
year = "2016",
month = "11",
day = "1",
doi = "10.1007/s12035-015-9486-6",
language = "English",
volume = "53",
pages = "5912--5927",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press",
number = "9",

}

TY - JOUR

T1 - Astrocytic CCAAT/Enhancer-Binding Protein Delta Contributes to Glial Scar Formation and Impairs Functional Recovery After Spinal Cord Injury

AU - Wang, Shao Ming

AU - Hsu, Jung Yu C

AU - Ko, Chiung Yuan

AU - Chiu, Nai En

AU - Kan, Wai Ming

AU - Lai, Ming Derg

AU - Wang, Ju Ming

PY - 2016/11/1

Y1 - 2016/11/1

N2 - 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.

AB - 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.

KW - Astrocyte migration

KW - Astrogliosis

KW - C/EBPδ

KW - MMP-3

KW - RhoA

UR - http://www.scopus.com/inward/record.url?scp=84945549825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84945549825&partnerID=8YFLogxK

U2 - 10.1007/s12035-015-9486-6

DO - 10.1007/s12035-015-9486-6

M3 - Article

C2 - 26510742

AN - SCOPUS:84945549825

VL - 53

SP - 5912

EP - 5927

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 9

ER -