Exercise-Derived Exosomal miR-151-3p: An Innovative Anti-inflammatory and Antioxidant Exerkine for Spinal Cord Injury
Exercise (Exe) training serves as the hub of the multimodal treatment system for spinal cord (SC) injury (SCI), with well-established efficacy. However, the forms in which it exerts its effects and the potential key mechanisms still require in-depth research. Exosomes (Exos) have demonstrated great potential in disease treatment and the elucidation of disease mechanisms. This experiment aims to investigate the functions and action targets of Exe-derived Exos (Exe-Exos) in SCI, providing a theoretical foundation for developing treatment strategies targeting Exos pathways post-SCI. Circulating blood Exos were extracted from normal Sprague-Dawley (SD) rats after 4-week treadmill Exe and from the control group (Sed). Hydrogel (Hyd) microneedles were employed to target and deliver the Exos to the T10 segment of the SC in rats with SCI. By constructing corresponding in vitro and in vivo cell and SCI animal models, we found that Exe-derived Exo miR-151-3p (Exe-Exos-miR-151-3p) mediated functional repair following SCI in rats. Furthermore, Exos were found to carry protective signals, with Exo-miR-151-3p as the key molecule. For the first time, we discovered that Exo-miR-151-3p produced anti-inflammatory (NF-kB signaling pathway), anti-apoptotic (Caspase3 and JNK), and anti- oxidative stress (Oxs)oxidative (Nrf2 and HO-1) effects by inhibiting the mitochondrial membrane gene ROMO1. Overall design: Then, we analyzed the gene expression profiles of RNA-seq from serum exosomes of 20 rats in Exercise group and 20 rats in Sedentary group.