SHED-Derived Exosomes Regulate Microglial Polarization in the Treatment of Traumatic Brain Injury in Rats via miR-330-5p

Abstract

Background: Traumatic brain injury (TBI) causes structural damage and impairs motor and cognitive function of the brain. Our previous study suggested that exosomes (EXs) secreted by stem cells from human exfoliated deciduous teeth (SHED) extenuated motor damage in TBI rats by regulating microglia. The molecular mechanism of SHED-EXs was investigated in the present study. Methods: The miRNA array was performed to determine the differential miRNA expression in SHED-EXs treating microglia. The key miRNA was selected. Flow cytometry, immunofluorescence, enzyme linked immunosorbent assay (ELISA) and Griess assay were performed to detect the function of key miRNA. Real-time PCR, Western blotting and dual luciferase reporter assay were used to confirm the relationship between key miRNA and the target gene. Chromatin immunoprecipitation (ChIP) was performed to determine the downstream pathway of EXs-miRNA. Traumatic brain injury rat model was established and local injection of EXs-miRNA was performed to evaluate the effect.Results: SHED-EXs delivery of miR-330-5p was the key in the regulation of microglia polarization by inhibiting M1 polarization and promoting M2 polarization. Mechanistically, miR-330-5p had an inhibitory effect on Ehmt2, and miR-330-5p/Ehmt2 promoted the transcription of CXCL14 through H3K9me2. In vivo data showed that SHED-EXs/miR-330-5p reduced neuro-inflammation and repaired neurological function of TBI rats. Conclusions: SHED-EXs/miR-330-5p improved the motor function of rats after TBI by inhibiting M1 polarization and promoting M2 polarization of microglia through Ehmt2/H3K9me2/CXCL14 pathway.