BMSC-Derived Exosomal miR-874-3p Protects against OGD/R-Induced Neuronal Injury in PC12 Cells via Regulating KPNA4

Sciatic nerve injury was considered to be one of the most common peripheral nerve injuries, posing a major threat to patients. miR-874-3p previously reported to modulate key biological processes including cell proliferation, immune response, and apoptosis. However, its specific role and underlying mechanism in sciatic nerve injury remain largely uncharacterized. In this study, we demonstrated that exosomal miR‑874‑3p derived from bone marrow mesenchymal stem cells (BMSCs) alleviates key pathological features of sciatic nerve injury in a cellular model.

BMSCs were isolated from Sprague Dawley rats and identified by Flow Cytometry (FCM). Exosomes were extracted from BMSCs using differential centrifugation. The morphology of BMSCs-derived exosomes was observed via TEM. The related gene and protein expression were respectively determined by qPCR and western blot. Cell viability and apoptosis were respectively assessed by CCK-8 kits and FCM. The level of ROS, MDA, SOD and GSH-Px were respectively detected using corresponding kit. Inflammatory factors were measured by ELISA. The dual-luciferase reporter assay served to determine the connection of miR-874-3p with KPNA4.

miR-874-3p was markedly upregulated in BMSCs-derived exosomes. The supplementation of BMSCs-Exos miR-874-3p maintained cell viability and diminished apoptosis. Moreover, it modulated the intracellular levels of oxidative stress-associated proteins within cells and concurrently suppressed the release of inflammatory factor, consequently decelerating neuronal impairment. Furthermore, the regulatory effects of BMSC-Exos miR-874-3p on cell proliferation, apoptosis, cytokine release, and oxidative stress were mediated by the inhibition of KPNA4, as evidenced by the fact that KPNA4 overexpression abolished these effects.

Exosomal miR‑874‑3p from BMSCs alleviated OGD/R‑induced neuronal injury by targeting KPNA4.