Astrocytic Cebpd Regulates Pentraxin 3 Expression to Promote Fibrotic Scar Formation After Spinal Cord Injury

Shao Ming Wang, Jung Yu C. Hsu, Chiung Yuan Ko, Hsiang En Wu, Yu Wei Hsiao, Ju Ming Wang

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Astroglial-fibrotic scars resulted from spinal cord injury affect motor and sensory function, leading to paralysis. In particular, the fibrotic scar is a main barrier that disrupts neuronal regeneration after spinal cord injury. However, the association between astrocytes and fibrotic scar formation is not yet understood. We have previously demonstrated that the transcriptional factor Cebpd contributes to astrogliosis, which promotes glial scar formation after spinal cord injury. Herein, we show that fibrotic scar formation was decreased in the epicenter region in Cebpd−/− mice after contusive spinal cord injury and astrocytic Cebpd promoted fibroblast migration through secretion of Ptx3. Furthermore, the expression of Mmp3 was increased under recombinant protein Ptx3 treatment in fibroblasts by observing microarray data, resulting in fibroblast migration. In addition, regulation of Mmp3 occurs through the NFκB signaling pathway by using an irreversible inhibitor of IκBα phosphorylation in pretreated fibroblasts. Of note, we used the synthetic peptide RI37, which blocks fibroblast migration and decreases fibroblast Mmp3 expression in IL-1β-treated astrocyte conditioned media. Collectively, our data suggest that fibroblast migration can be affected by astrocytic Cebpd through the Ptx3/NFκB/Mmp3 axis pathway and that the RI37 peptide may act as a therapeutic medicine to inhibit fibrotic scar formation after spinal cord injury.

Original languageEnglish
Pages (from-to)2200-2208
Number of pages9
JournalMolecular Neurobiology
Volume60
Issue number4
DOIs
Publication statusAccepted/In press - 2023

Keywords

  • Astrocyte
  • Cebpd
  • Fibrotic scar
  • Ptx3
  • Spinal cord injury

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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