circRNA_013145-miR-185-5p-RhoA axis: A novel mechanism in the pathophysiology of diabetes-induced erectile dysfunction

Abstract

Diabetes mellitus-induced erectile dysfunction (DMED) is a common diabetic complication characterized by endothelial dysfunction and corpus cavernosum (CC) remodeling. Although circular RNAs (circRNAs) have been implicated in diabetic vascular diseases, their roles in DMED remain largely unknown. The present study investigated the biological function and underlying mechanism of circRNA_013145 in DMED. CircRNA microarray analysis identified circRNA_013145 as a significantly upregulated circRNA in penile tissue from DMED rats. Its biological function was evaluated using loss-of-function and rescue experiments in high glucose (HG)-treated CC smooth muscle cells (CCSMCs), human umbilical vein endothelial cells (HUVECs) and a DMED rat model. circRNA_013145 expression was markedly increased in DMED penile tissue and HG-treated cells. circRNA_013145 knockdown attenuated HG-induced oxidative stress, inflammation, apoptosis, autophagy and phenotypic transformation, while improving endothelial function and cell viability. Mechanistically, circRNA_013145 served as a molecular sponge for miR-185-5p, thereby positively regulating RhoA expression. Rescue experiments demonstrated that inhibition of miR-185-5p partially abolished the protective effects of circRNA_013145 knockdown. Furthermore, adenovirus-mediated knockdown of circRNA_013145 significantly improved erectile function and alleviated cavernosal pathological injury in DMED rats, as evidenced by an increased intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio, enhanced CD31 expression and reduced collagen deposition. In conclusion, circRNA_013145 promotes the progression of DMED through the miR-185-5p/RhoA axis. Targeting circRNA_013145 may represent a potential therapeutic strategy for DMED.