Exosomes Derived from miR-301a-3p-Modified Adipose-derived Mesenchymal Stem Cells Reverse Hypoxia-induced Erectile Dysfunction in Rat Models

Abstract

Erectile dysfunction (ED) has often been observed in patients with obstructive sleep apnea (OSA). Research on adipose-derived stem cells (ADSCs)-derived exosomes has shown that they have significant therapeutic effects in many diseases including ED. In this study, ED was induced in Sprague Dawley (SD) rats using chronic intermittent hypoxia (CIH) exposure. CIH-mediated influences were then measured in the corpus cavernous smooth muscle cells (CCSMCs). Results showed that miR-301a-3p-enriched exosomes treatment significantly recovered erectile function in rats and CCSMCs by promoting autophagy and inhibiting apoptosis. The treatment also significantly recovered the level of alpha Smooth Muscle Actin (α-SMA) in rats and CCSMCs. Bioinformatics predicted that Phosphatase and tensin homolog (PTEN) and Toll-like receptor 4 (TLR4) might be targets of miR-301a-3p. Our results indicate that PTEN-overexpression vectors or TLR4-overexpression vectors reverse the therapeutic effects achieved by miR-301a-3p in CCSMCs indicating that PTEN/HIF-1α and TLR4 signaling pathways play key roles in the progression of ED. The findings in this study suggest that miR-301a-3p should be considered as a new therapeutic target for treating ED associated with OSA.