Protective effect and potential mechanism of Schwann cell‐derived exosomes on mechanical damage of rat dorsal root ganglion cells

Abstract

Pudendal nerve (PN) injury was one of the most important pathogenesis of stress urinary incontinence (SUI). Schwann cell (SC)-derived exosomes could promote axonal regeneration. Wnt protein could significantly promote axonal regeneration and participate in the regulation of proliferation and differentiation of neural stem cells. Therefore, we sought to determine whether SCs-derived exosomes might also protect against damaged dorsal root ganglion cells (DRGs) through the Wnt/β-catenin pathway. The DRGs injury model was fabricated using a four-point bending system. The exosomes were separated from the SCs supernatant. XAV939, which was a small molecule inhibitor, was used to inhibit the Wnt/β-catenin pathway. Next, Cell Counting Kit-8 (CCK8) kit was used to detect cell activity. We evaluated the proliferative activity of DRG cells using the cell cycle and apoptosis detection kit. We assessed the cell apoptotic rates through the Annexin V/PE double staining. Finally, we detect the expression of downstream proteins of Wnt/β-catenin pathway in DRG cells using western blotting. SC-derived exosomes had protective effects on DRGs after mechanical damage, which could promote cell proliferation, transition of the cell cycle to the G2 phase, and inhibit cell apoptosis. Exogenous administration of XAV939 suppressed the promoting effect of SCs -derived exosomes on DRG cells and the expression of downstream proteins of Wnt/β-catenin pathway in DRG cells was also suppressed. These results suggested that SC-derived exosomes have a repairing effect on DRG cells injury caused by cyclic mechanical stretching (CMS) and the Wnt/β-catenin pathway is potentially involved in the process.