Reactive astrocytes in glial scar attract olfactory ensheathing cells migration by secreted TNF-α in spinal cord Lesion Of Rat

Zhida Su, Yimin Yuan, Jingjing Chen, Li Cao, Yanling Zhu, Liang Gao, Yang Qiu, Cheng He

Research output: Contribution to journalArticle

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Abstract

Background: After spinal cord injury (SCI), the formation of glial scar contributes to the failure of injured adult axons to regenerate past the lesion. Increasing evidence indicates that olfactory ensheathing cells (OECs) implanted into spinal cord are found to migrate into the lesion site and induce axons regeneration beyond glial scar and resumption of functions. However, little is known about the mechanisms of OECs migrating from injection site to glial scar/lesion site. Methods and Findings: In the present study, we identified a link between OECs migration and reactive astrocytes in glial scar that was mediated by the tumor necrosis factor-α (TNF-α). Initially, the Boyden chamber migration assay showed that both glial scar tissue and reactive astrocyte-conditioned medium promoted OECs migration in vitro. Reactive astrocytederived TNF-α and its type 1 receptor TNFR1 expressed on OECs were identified to be responsible for the promoting effect on OECs migration. TNF-α-induced OECs migration was demonstrated depending on activation of the extracellular signalregulated kinase (ERK) signaling cascades. Furthermore, TNF-α secreted by reactive astrocytes in glial scar was also showed to attract OECs migration in a spinal cord hemisection injury model of rat. Conclusions: These findings showed that TNF-α was released by reactive astrocytes in glial scar and attracted OECs migration by interacting with TNFR1 expressed on OECs via regulation of ERK signaling. This migration-attracting effect of reactive astrocytes on OECs may suggest a mechanism for guiding OECs migration into glial scar, which is crucial for OECsmediated axons regrowth beyond the spinal cord lesion site.

Original languageEnglish (US)
Article numbere8141
JournalPLoS One
Volume4
Issue number12
DOIs
StatePublished - 2009

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tumor necrosis factors
astrocytes
neuroglia
cell movement
spinal cord
Neuroglia
Astrocytes
lesions (animal)
Cell Movement
Cicatrix
Rats
Spinal Cord
Tumor Necrosis Factor-alpha
rats
Receptors, Tumor Necrosis Factor, Type I
axons
Axons
Spinal Cord Injuries
cells
phosphotransferases (kinases)

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Reactive astrocytes in glial scar attract olfactory ensheathing cells migration by secreted TNF-α in spinal cord Lesion Of Rat. / Su, Zhida; Yuan, Yimin; Chen, Jingjing; Cao, Li; Zhu, Yanling; Gao, Liang; Qiu, Yang; He, Cheng.

In: PLoS One, Vol. 4, No. 12, e8141, 2009.

Research output: Contribution to journalArticle

Su, Zhida ; Yuan, Yimin ; Chen, Jingjing ; Cao, Li ; Zhu, Yanling ; Gao, Liang ; Qiu, Yang ; He, Cheng. / Reactive astrocytes in glial scar attract olfactory ensheathing cells migration by secreted TNF-α in spinal cord Lesion Of Rat. In: PLoS One. 2009 ; Vol. 4, No. 12.
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