MiR-369-3p Regulates Microglia Polarization and Neuroinflammation in Traumatic Spinal Cord Injury by Targeting PELI1.

ABSTRACT: Study DesignConducted in vivo and in vitro modeling investigations.ObjectiveThe present research aims to explore the regulatory role of microRNA (miR)-369-3p in spinal cord injury inflammatory response and its targeting mechanism.MethodsA female mouse model with T8-T10 spinal cord injury (SCI) was established. The motor function assessment (BMS) score was employed to evaluate motor function. BV2 microglial cells were treated with lipopolysaccharide (LPS) in vitro to construct an inflammatory cell model. Real-time fluorescence quantitative PCR was applied to assess miR-369-3p, M1 (CD86, iNOS), and M2 (Arg-1) polarization markers. Enzyme-linked immunosorbent assay (ELISA) determined the concentration of inflammatory factors (TNF-α, IL-6, and IL-1β). Additionally, RNA pull-down, RNA immunoprecipitation, and Dual-luciferase reporter experiments were performed to verify that miR-369-3p targets Pellino E3 ubiquitin protein ligase 1 (PELI1).ResultsmiR-369-3p was noticeably down-regulated in SCI mice spinal cord tissues and LPS-induced BV2 cells, while PELI1 expression was upregulated. Raising miR-369-3p improved BMS scores (for moto function) and reduced inflammatory cytokines in spinal cord tissues. Mechanistically, miR-369-3p targeted PELI1. LPS treatment increased inflammatory factor mRNA levels and concentrations, which were significantly reversed by raising miR-369-3p and restored by PELI1. Also, raising miR-369-3p suppressed CD86 and iNOS and induced Arg-1 expression in LPS-activated microglia, while PELI1 reversed this effect.ConclusionmiR-369-3p mitigates inflammation and suppresses microglia polarization by targeting PELI1, ultimately mitigating the progression of spinal cord injury. Our research suggests miR-369-3p as a potential therapeutic target for spinal cord injury.

SUBMITTER: Li Y 

PROVIDER: S-EPMC12759018 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature