Caveolin-1 scaffolding domain-derived peptide enhances the antiapoptotic progresses of corpus cavernosum smooth muscle cells after cavernous nerve injury

Abstract

Abstract Increased apoptosis in penis due to cavernous nerve injury (CNI) is a crucial contributor to erectile dysfunction (ED). Caveolin-1 scaffolding domain (CSD)-derived peptide (CSD peptide) has been found to exhibit potential antiapoptotic property. However, it remains unknown whether CSD peptide therapy can alleviate the apoptosis of corpus cavernosum smooth muscle cells (CCSMCs), and ED in CNI rats. We aimed to validate the assumption that CSD peptide may promote the improvement of bilateral CNI-induced ED (BCNI-ED) by enhancing the antiapoptotic processses of CCSMCs. Fifteen 10-week-old male Sprague-Dawley (SD) rats were assigned into three groups at random: sham surgery (Sham) group and BCNI groups that underwent saline or CSD peptide treatment respectively. At 3 weeks postoperatively, erectile function (EF) was assessed. Then, processed penis was histologically examined. To investigate the mechanism of action of CSD peptide in treating BCNI-ED, an in vitro model of CCSMC apoptosis was established using transforming growth factor-beta 1 (TGF-β1). In BCNI rats, CSD peptide significantly prevented ED, raised the phosphorylation of AKT, and decreased the expressions of Bax/Bcl-2 ratio, caspase3, and the quantity of apoptotic cells. TGF-β1-treated CCSMCs exhibited lower levels of p-AKT, mitochondrial membrane potential (MMP), superoxide dismutase (SOD), and cell viability, along with higher levels of Bax/Bcl-2 ratio, apoptotic index, reactive oxygen species (ROS), and malondialdehyde (MDA). However, CSD peptide partially restored these alterations. Consequently, BCNI-ED may be prevented in part by CSD peptide-mediated reduction of CCSMC apoptosis, which further promotes the development of CSD peptide as an effective therapy for pRP-ED.