LAUSR

INTRODUCTION AND OBJECTIVE: Erectile dysfunction (ED) is one of most common complications in men with diabetes. ED in these men occurs at early age and present with severe symptoms. Besides, PDE5i, a commonly used drug for ED, has poor efficacy on diabetic erectile dysfunction (DMED) due to the corporal fibrosis. Studies have suggested that exosomes play an important role in the process of intercellular communication and pathological changes, so it may become a new method for the treatment of DMED. In this study, we investigated whether exosomes derived from corpus cavernosum smooth muscle cells (CCSMC) could improve DMED via alleviating fibrosis and modulating the TGF-b1/Smad2/3/CTGF signaling pathways. METHODS: Exosomes were extracted by ultracentrifugation and identified by transmission electron microscope. In cell experiments, the enrichment ability of CCSMC derived exosomes (CCSMCs-Ex) and mesenchymal stem cell derived exosomes (MSCs-Ex) in target cells was compared by confocal microscope. In animal experiments, the retention time of CCSMCs-Ex and MSCs-Ex in the penis of DMED rats was compared by in vivo imaging techniques after the intracavernous injection. The erectile function was assessed by electrical stimulation. The content of a-SMA and collagen and TGF-b1/Smad2/3/CTGF expression levels in tissues were determined by western blotting and histological studies. RESULTS: We have demonstrated that CCSMC can secrete exosomes for the first time through the extraction and identification of exosomes. Subsequently, cell experiments showed that CCSMCs-Ex was taken faster by cells compared to MSCs-Ex. Animal experiments showed that CCSMCs-Ex was easier to stay in DMED rats' penises compared to MSCs-Ex. Electrophysiological experiments showed that the erectile function of DMED rats injected with CCSMCs-Ex was improved. Meanwhile, we found that CCSMCs-Ex can increase the ratio of a-SMA and collagen in the cavernous tissue by inhibiting the TGF-b1/Smad2/3/CTGF pathway, thereby reducing the DM-induced penile fibrosis. CONCLUSIONS: We demonstrated for the first time that CCSMC can secrete exosomes and CCSMCs-Ex has good enrichment ability in vivo and in vitro. CCSMCs-Ex exerts anti-fibrotic effects in DMED by inhibiting the TGF-b1/Smad2/3/CTGF pathway. Our research indicates that CCSMCs-Ex may be an effective tool for the treatment of DMED, which provides a theoretical basis for the breakthrough in the treatment of DMED.