Abstract
BackgroundErectile dysfunction (ED) has often been observed in patients with obstructive sleep apnea (OSA). Research on adipose-derived mesenchymal stem cell (ADSC)-derived exosomes has shown that they have significant therapeutic effects in many diseases including ED.MethodsIn 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).ResultsOur data showed that miR-301a-3p-enriched exosome 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.ConclusionsOur results indicate that PTEN-overexpression vectors or TLR4-overexpression vectors reverse the therapeutic effects achieved by miR-301a-3p in CCSMCs indicating that PTEN/hypoxia-inducible factor-1 alpha (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 a new therapeutic target for treating ED associated with OSA.
Highlights
Erectile dysfunction (ED), known as inadequate penile erection, is a common clinical entity that mainly affects males older than 40 years [1]
Exosome treatment increased the level of autophagy through overexpressing LC3I/II and p65 while the levels of p62 decreased with miR-301a-3p-enriched exosomes having a more pronounced effect (Fig. 4c, e)
These results suggest that phosphatase and tensin homolog (PTEN) and Toll-like receptor 4 (TLR4) can be directly targeted by miR-301a-3p
Summary
Erectile dysfunction (ED), known as inadequate penile erection, is a common clinical entity that mainly affects males older than 40 years [1]. Several factors are associated with ED including smoking, hormonal imbalance, general health status of the individual, diabetes mellitus, cardiovascular diseases, obstructive sleep apnea (OSA), and psychiatric disorders [4, 5]. Chronic intermittent hypoxia (CIH) is one of the most important and direct consequences of obstructive sleep apnea [6, 7] with studies showing a higher ED incidence in male patients with chronic hypoxia [8]. Erectile dysfunction (ED) has often been observed in patients with obstructive sleep apnea (OSA). Research on adipose-derived mesenchymal stem cell (ADSC)-derived exosomes has shown that they have significant therapeutic effects in many diseases including ED
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