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

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 w...

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Autores principales: Liang, Li, Zheng, Dachao, Lu, Chao, Xi, Qinghong, Bao, Hua, Li, Wengfeng, Gu, Yufei, Mao, Yuanshen, Xu, Bin, Gu, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836493/
https://www.ncbi.nlm.nih.gov/pubmed/33494812
http://dx.doi.org/10.1186/s13287-021-02161-8
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author Liang, Li
Zheng, Dachao
Lu, Chao
Xi, Qinghong
Bao, Hua
Li, Wengfeng
Gu, Yufei
Mao, Yuanshen
Xu, Bin
Gu, Xin
author_facet Liang, Li
Zheng, Dachao
Lu, Chao
Xi, Qinghong
Bao, Hua
Li, Wengfeng
Gu, Yufei
Mao, Yuanshen
Xu, Bin
Gu, Xin
author_sort Liang, Li
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02161-8.
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spelling pubmed-78364932021-01-26 Exosomes derived from miR-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models Liang, Li Zheng, Dachao Lu, Chao Xi, Qinghong Bao, Hua Li, Wengfeng Gu, Yufei Mao, Yuanshen Xu, Bin Gu, Xin Stem Cell Res Ther Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02161-8. BioMed Central 2021-01-25 /pmc/articles/PMC7836493/ /pubmed/33494812 http://dx.doi.org/10.1186/s13287-021-02161-8 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liang, Li
Zheng, Dachao
Lu, Chao
Xi, Qinghong
Bao, Hua
Li, Wengfeng
Gu, Yufei
Mao, Yuanshen
Xu, Bin
Gu, Xin
Exosomes derived from miR-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models
title Exosomes derived from miR-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models
title_full Exosomes derived from miR-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models
title_fullStr Exosomes derived from miR-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models
title_full_unstemmed Exosomes derived from miR-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models
title_short Exosomes derived from miR-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models
title_sort exosomes derived from mir-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836493/
https://www.ncbi.nlm.nih.gov/pubmed/33494812
http://dx.doi.org/10.1186/s13287-021-02161-8
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