Phenotypic modulation of corpus cavernosum smooth muscle cells in type 2 diabetic rats is mediated by regulated exosomes secretion via neutral sphingomyelinase-2

Phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMCs) is closely related to the occurrence of erectile dysfunction (ED). However, the effect of exosomes (EXOs) on the phenotypic modulation of CCSMCs with diabetes mellitus (DM)-related ED is not fully understood. Using a rat model of type 2 DM, we found an important role for phenotypic modulation of CCSMCs in DM-related ED. EXO secretion by CCSMCs is also driven by pathological changes to the corpus cavernosum in diabetic rats. We used CCSMCs subjected to platelet-derived growth factor-BB as an in vitro model of phenotypic modulation and isolated EXOs from the supernatants of cultured CCSMCs by ultracentrifugation. The results suggest that phenotypic modulation enhances the capacity of CCSMCs to secrete EXOs and that inhibiting EXO secretion could restore the contractile phenotype of CCSMCs in vitro. Notably, a further mechanistic study revealed that regulated EXO secretion could change the phenotype of CCSMCs via the neutral sphingomyelinase-2 (nSMase2) pathway. Taken together, our results indicate that the modulation of EXO biogenesis and secretion may be a novel therapeutic approach to improve type 2 DM-induced ED by maintaining the contractile phenotype of CCSMCs.