Pentraxin 3-Induced Fibrotic Scar Formation via Astrocytic Cebpd activation after Spinal Cord Injury

Abstract

Astroglial-fibrotic scars after spinal cord injury affect motor and sensory function, leading to paralysis. Especially, fibrotic scar is a main barrier to disrupt neuronal regeneration after spinal cord injury. However, the association between astrocyte and fibrotic scar formation has not yet been understanding. According to our previous study showed that transcriptional factor Cebpd contributes to astrogliosis that promote glial scar formation after spinal cord injury. Herein, we show that fibrotic scar formation was decreased in epicenter region in Cebpd−/− mice after contusive spinal cord injury. Further, astrocytic Cebpd promotes fibroblast migration through secretion of Ptx3. We also found that expression of Mmp3 was increased under recombinant protein Ptx3 treatment in fibroblast by observing microarray data, resulting in fibroblast migration. Furthermore, regulation of Mmp3 is through NFκB signaling pathway by using an irreversible inhibitor of IκBα phosphorylation-pretreated fibroblast. Of note, we use synthetic peptide RI37 showing that block fibroblast migration and decrease fibroblast Mmp3 expression under IL-1β-treated astrocyte conditional media. Collectively, our data suggest that the fibroblast migration can be affected by astrocytic Cebpd through Ptx3/NFκB/Mmp3 axis pathway and RI37 peptide may act as a therapeutic medicine to inhibit fibrotic scar formation after spinal cord injury.