(275) IGFBP5 Short Hairpin RNA (shRNA) Constructs Improve Erectile Function in a Mouse Model of Cavernous Nerve Injury

Abstract

Abstract Introduction Radical prostatectomy for prostate cancer not only induces cavernous nerve injury but also causes cavernous angiopathy, which is responsible for poor responsiveness to phosphodiesterase-5 inhibitors. Insulin-like growth factor-binding protein 5 (IGFBP5) promotes cell death and induces apoptosis in various cell types. Objective To investigate the effectiveness of IGFBP5 knockdown at improving erectile function in a mouse model of cavernous nerve injury. Methods Eight-week-old C57BL/6 mice were used to prepare cavernous nerve injury model. Mice were divided into 4 groups: a sham operation group and three cavernous nerve injury (CNI) groups, which were administered intracavernous injections of phosphate buffered saline, scrambled control shRNA, or shRNA targeting mouse IGFBP5 (shIGFBP5) lentivirus particles. One week later, we measured erectile function by electrically stimulating the bilateral cavernous nerve. Results IGFBP5 expression in cavernous tissues were significantly increased in CNI mice compare to sham mice. CNI mice had reduced erectile function, but shIGFBP5 treatment resulted in significant improvements. Furthermore, in CNI mice, numbers of cavernous endothelial cells, pericytes, and neuronal cells were increased by shIGFBP5 treatment. Conclusions Knockdown of IGFBP5 improved erectile function in CNI mice by enhancing neurovascular regeneration. Local inhibition of IGFBP5 expression may provide a new treatment strategy for the treatment of neurovascular diseases. Disclosure No.