Oligodendrocyte Progenitor Cells Increase Chi3l1 Secretion in exosome to Activate Myh9 and Promote Proliferation through Connexin47 Connected to Astrocytes

Abstract Background: Neurodegenerative diseases, caused by the loss of neurons or myelin sheath, are some of the most important neurological diseases that threaten the health of the elderly. In the CNS, oligodendrocytes (OLs) are the only cells that can form myelin. Astrocytes (ASTs) play a generally beneficial role in remyelination, including the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) to OLs. However, the specific downstream mechanism is unclear.Methods: This study investigated the proliferation of OPCs in OPCs mono-culture, OPCs culture with ASTs supernatant, and ASTs-OPCs co-culture. Gene Ontology (GO) analysis were used to analyze the differentially expressed genes after transcriptome sequencing of these OPCs. Electron microscope, Nanoparticle Tracking Analysis (NTA), Fluorescence tracing of exosomes and Western blot were used to evaluate the effects of exsomes. Pull-down, co-immunoprecipitation (Co-IP) and mass spectrometry analys were conducted to find the downstream signal proliferation which is transmitted information into OPCs.Reasults: Direct contact co-culture of ASTs and OPCs promotes the proliferation of OPCs. After Cx47 siRNA interference under ASTs-OPCs co-culture, Chi3l1 secretion in exosome reveals associated decrease, and OPCs proliferation decreased. The cell proliferation induced by Chi3l1 was inhibited after siRNA interfered with Myh9, and the expression of cyclin D1 was also decreased.Conclusions: These results suggest that ASTs transmit information to OPCs by increasing gap junction channel Cx47, thereby promoting the secretion of Chi3l1 in exosome of OPCs. The secretory form of Chi3l1 in exosome might be easier to enter the target cell than in extracellular supernatant, which is beneficial to the activation of Myh9 to promote OPCs proliferation. This may be a potential target for drugs rescuing neurodegeneration diseases related to remyelination.