(061) Xenon Facilitates Schwann Cell Demyelination via Inhibition of SPRY2 in Treating Erectile Function After Cavernous Nerve Injury

Abstract

Abstract Introduction Cavernous nerve injury induced erectile dysfunction (ED) is the most common complication after radical prostatectomy for prostate cancer. Our previous studies found that xenon (Xe) can partially restore the erectile function and cavernous nerve function of rats with neurogenic ED, but the mechanism is unclear. Schwann cells (SC) play an important role in peripheral nerve repair, and after axonal injury, SC undergo demyelination and transform into repair-type SC to promote repair. Objective The purpose of this study is to verify whether Xe promotes the demyelination of Schwann cells and its molecular mechanism. Methods Human SCs were cultured in vitro and given Echo-lipid particles (ELIPs) carrying Xe. The control group was given empty ELIPs. Ultrasound was performed above the culture dish to break ELIPs and release the gas. After treatment, the expression level of the EGR2 gene, a marker of SC demyelination, was detected, and RNA was extracted for mRNA sequencing. Sequencing results were validated in SC and rat dorsal root ganglion (MRP) tissues through Western blot and qPCR. Results After Xe treatment, the level of EGR2 in SC cultured in vitro decreased, indicating that Xe treatment can promote the demyelination process of SC. RNA-sequencing results showed that after Xe treatment, 88 genes were up-regulated and 231 genes were down-regulated. Top 10 KEGG pathway enrichment analysis suggested an increase in MAPK pathway expression. Meanwhile, among the differentially expressed genes, we found that the expression of SPRY2 (Sprouty RTK Signaling Antagonist 2) decreased, a negative feedback regulator of the MAPK pathway. Using qPCR and Western blot on SC and rat MPG tissues in vitro, we validated the sequencing results and found that after Xe treatment, the expression level of SPRY2 decreased, and the level of pERK increased. Conclusions Xe may promote the demyelination of Schwann cells and the repair of cavernous nerves by inhibiting the SPRY2 level of SC, reducing its inhibition of the MAPK/ERK pathway. Disclosure No.