CSPGs promote the migration of meningeal fibroblasts via p38 mitogen-activated protein kinase signaling pathway under OGD conditions

Abstract

AimsUsually glial scar that occurs after central nervous system injury has significantly affected the local neural microenvironment. Meningeal fibroblasts play an essential role in the formation of the glial scar. However, how and why meningeal fibroblasts migrate to lesion sites is still unclear. Main methodsAstrocytes were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) injury. And then, we measured the glial fibrillary acidic protein(GFAP) and chondroitin sulfate proteoglycans (CSPGs) expression of reactive astrocytes by western blot and quantitative polymerase chain reaction (qPCR) after they were co-cultured with meningeal fibroblasts. Following, we clarified the possibility that CSPGs induce the migration of meningeal fibroblasts to glial scar by transwell migration assay and the activation of the p38 MAPK signaling pathway during the migration by western blot. Key findingsWe found that co-cultured meningeal fibroblasts could alleviate the significantly increased expression of GFAP and CSPGs in the activation of reactive astrocytes induced by OGD/R. Additionally, CSPGs secreted by reactive astrocytes could induce the migration of meningeal fibroblasts and the expression of phospho-p38 in meningeal fibroblasts when meningeal fibroblasts were co-cultured with supernatant of reactive astrocytes. What's more, we could observe a noticeable increase in CSPGs that chondroitinase ABC could reverse their functions. Moreover, phospho-p38 could cause the expression of phospho-cofilin and the migration of CSPGs-induced meningeal fibroblasts. SignificanceOur study provides reliable evidence for explaining scar formation mechanisms and further studying to improve regeneration after an injury to the central nervous system.