Exosomal lncRNA MIAT enriched in M2 macrophages contributes to electroacupuncture-driven peripheral nerve regeneration through targeting MiR-130a-3p/KLF7

Aims Electroacupuncture (EA) promotes the regeneration and repair of peripheral nerve injury (PNI) in clinical, and its underlying neuroimmune mechanisms have still not been fully clarified. Our study investigates the role of exosomal lncRNA MIAT in EA-mediated repair of PNI. Methods The study observed EA’s effect on PNI in a rat model established by sciatic nerve injuries. The sciatic nerve function was observed via sciatic nerve function index. Serum exosomal and sciatic nerve lncRNA MIAT levels were quantified, macrophage polarization was detected via immunofluorescence. Interventions included local lentiviral lncRNA MIAT overexpression (LV-MIAT), adeno-associated virus-mediated lncRNA MIAT knockdown (AAV-siMIAT), and GW4869 (exosome inhibitor) injection. Neuronal cells were transfected with miR-130a-3p mimics/inhibitors or LV-MIAT, and lncRNA MIAT/miR-130a-3p/KLF7 interactions were confirmed via dual-luciferase assays. Results EA intervention promotes peripheral nerve functional recovery in PNI rats, enhances axonal density, increases M2 macrophage number, and exosomal lncRNA MIAT level. M2-Exo administration in neuron promoted nerve cells viability and neurite length, while siMIAT/GW4869 partially reversed these effects. More, lncRNA MIAT acted as a miR-130a-3p sponge, relieving its repression of KLF mRNA and protein levels. Overexpressing lncRNA MIAT or silencing miR-130a-3p activated KLF7 expression, enhancing neuronal survival and axon regeneration. Conclusion EA intervention improved PNI, restored neuronal function, increased PNI area M2 macrophage polarization and regulated lnc MIAT/miR-130a-3p/KLF7 axis expression.