Exosomes secreted by adipose mesenchymal stem cells overexpressing circPIP5K1C exert

Erectile dysfunction (ED) seriously affects men's normal life, and obstructive sleep apnoea (OSA) has been diagnosed as a causative factor. Currently, exosomes secreted by adipose mesenchymal stem cells (ADSC) have been used in the non-clinical experimental treatment of ED disease with prominen...

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Veröffentlicht in:Biochimica et biophysica acta. Molecular basis of disease 2024-08, Vol.1870 (6), p.167223, Article 167223
Hauptverfasser: Gu, Xin, Liang, Li, Lu, Chao, Wang, Jiangyi, Hua, Bao, Li, Wengfeng, Mao, Yuanshen, Yang, Qing, Xu, Bin
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Sprache:eng
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Zusammenfassung:Erectile dysfunction (ED) seriously affects men's normal life, and obstructive sleep apnoea (OSA) has been diagnosed as a causative factor. Currently, exosomes secreted by adipose mesenchymal stem cells (ADSC) have been used in the non-clinical experimental treatment of ED disease with prominent efficacy due to the advantages of high stability and no immune exclusion. In this study, chronic intermittent hypoxia (CIH) exposure was used to induce ED-corresponding phenotypes in Sprague Dawley (SD) rats as well as in cavernous smooth muscle cells (CCSMCs). ED symptoms were treated using exosomes secreted by ADSCs overexpressing circPIP5K1C (EXO-circ) injected into the rat corpus cavernosum. EXO-circ has the effect of ameliorating ED induced by CIH exposure in rats, the mechanism of which is to promote the expression of the downstream target gene SMURF1 after adsorption of miR-153-3p through the sponge so that SMURF1 and PFKFB3 occur protein-protein binding and ubiquitination degradation of PFKFB3 appears to inhibit the occurrence of spongiotic smooth muscle cells glycolysis, and to restore the function of the smooth muscle. These findings show that EXO-circ have a promising therapeutic potential in OSA-induced ED. [Display omitted] •Association between OSA and ED: The study establishes a significant link between obstructive sleep apnoea (OSA) and erectile dysfunction (ED), highlighting the impact of OSA on men's overall well-being.•Utilization of Exosomes from ADSC: The research leverages the use of exosomes derived from adipose mesenchymal stem cells (ADSC) in the experimental treatment of ED. These exosomes demonstrate notable efficacy attributed to their high stability and immune-exclusion-free properties.•CIH Exposure Model: Chronic intermittent hypoxia (CIH) exposure is employed to induce ED-related phenotypes in both Sprague Dawley (SD) rats and cavernous smooth muscle cells (CCSMCs), providing a relevant experimental model for studying ED.•Overexpression of circPIP5K1C in ADSC Exosomes: The study introduces exosomes secreted by ADSCs with overexpressed circPIP5K1C (EXO-circ), which are administered into the rat corpus cavernosum to alleviate ED symptoms induced by CIH exposure.•Mechanism of Action: EXO-circ demonstrates its therapeutic effect by promoting the expression of the downstream target gene SMURF1. This occurs after the adsorption of miR-153-3p through the sponge mechanism. Subsequently, SMURF1 engages in protein-protein binding with PFKFB3, le
ISSN:0925-4439
1879-260X
1879-260X
DOI:10.1016/j.bbadis.2024.167223