Therapeutic potential of mesenchymal stem cell-derived exosomal miR-296-5p and miR-337-3p in age-related erectile dysfunction via regulating PTEN/PI3K/AKT pathway
Kefan Li, Ruiyu Li, Zongyong Zhao, Feng Chen, Shuai Liu, Qiang Fu
Abstract
Mesenchymal stem cells (MSCs) are viewed as an increasingly promising treatment for age-related erectile dysfunction (AED). Owing to the limitations of injecting living cells, the injection of exosomes appears to be a more plausible option. However, whether MSC-derived exosomes (MSC-Exos) improve AED and their potential mechanism remains unknown. MSC-Exos were prepared and injected intracavernously into aged rats to determine their effects on AED. Masson's trichrome staining was used to ascertain the changes in the histological structure of the corpus cavernosum. Then miRNA sequencing of MSC-Exos and analysis of the critical exosomal miRNAs were performed, as well as their target pathway enrichment analysis. Real-time quantitative PCR (RT-qPCR) and Western blot assay were performed to reveal the functions of MSC-Exos in regulating the PTEN/PI3K/AKT signaling pathway. Moreover, the effects of MSC-Exos on the corpus cavernosum smooth muscle cells (CCSMCs) apoptosis are explored in vitro. The experimental data validate that intracavernous injection of MSC-Exos ameliorated erectile function in AED rats. Masson's trichrome staining shows MSC-Exos therapy restores the histological structure of the corpus cavernosum by improving the ratios of smooth muscle to collagen. The exosomal miR-296-5p and miR-337-3p target and inhibit PTEN, modulating the PI3K/AKT signaling pathway. Furthermore, exosomes inhibit the apoptosis of CCSMCs. Our findings suggest that MSC-Exos improve AED by delivering miR-296-5p and miR-337-3p to regulate the PTEN/PI3K/AKT signaling pathway. These results bode well for the therapeutic potential of MSC-Exos for AED treatment.