Exosomes derived from miR-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models

Abstract

Background 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. Methods 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 Our 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. Conclusions 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/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.

Adipose stem cells-released extracellular vesicles as a next-generation cargo delivery vehicles: a survey of minimal information implementation, mass production and functional modification

“…THE modified strategies for enhancing loading and targeted delivery of EVs have been reported. Engineering EVs were mostly carried out either via transfecting functional molecules into ASCs [ 14 , 17 , 21 , 26 , 34 , 35 , 44 , 45 , 49 , 72 , 77 , 79 , 82 , 113 , 125 , 181 ] or directly transfecting functional molecules into EVs [ 22 , 37 , 142 ]. Six studies [ 20 , 67 , 85 , 86 , 102 , 103 ] reported the strategy of hypoxia culture precondition of ASCs.…”

Erectile Dysfunction and Obstructive Sleep Apnea: A Review

“…The same group in 2015 demonstrated that endoplasmic reticulum stress-related cell apoptosis is involved with low levels of constitutive NOS and NO in rats ( 44 ). Recently, Liang et al ( 45 ) showed that exosome treatment significantly improved erectile function in LTIH exposure-induced ED rats and corpus cavernous smooth muscle cells (CCSMCs) by inhibiting apoptosis and promoting autophagy, which were associated with the PTEN/hypoxia-inducible factor-1 alpha (HIF-1α) and Toll-like receptor 4 (TLR4) signaling pathways.…”

Autophagy: a multifaceted player in the fate of sperm

“…Interestingly, the overexpression of PTEN or TLR4 reverses the therapeutic effects of miR-301a-3p in CCSMCs, indicating that miR-301a-3p modulates PTEN/HIF-1α/TLR4 signaling, autophagy and apoptosis for the treatment of ED. However, the cross-talk of PTEN/HIF-1α/TLR4 signaling and autophagy remains to be further investigated in ED ( Liang et al , 2021 ).…”