Mitochondria-Rich Microvesicles Alleviate CNI ED by Transferring Mitochondria and Suppressing Local Ferroptosis
Zhenkang Liang,* Zehong Chen,* Chaowei Zhang, Cui Chen, Wende Yang, Yuxuan Zhang, Hongbo Wei Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China*These authors contributed equally to thi...
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2024-11-01
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| author | Liang Z Chen Z Zhang C Chen C Yang W Zhang Y Wei H |
| author_facet | Liang Z Chen Z Zhang C Chen C Yang W Zhang Y Wei H |
| author_sort | Liang Z |
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| description | Zhenkang Liang,* Zehong Chen,* Chaowei Zhang, Cui Chen, Wende Yang, Yuxuan Zhang, Hongbo Wei Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongbo Wei, Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road 600, Guangzhou, 510630, People’s Republic of China, Tel +86-020-85253000, Email weihb@mail.sysu.edu.cnPurpose: Erectile dysfunction (ED) frequently arises as a complication of pelvic surgeries, including rectal and prostate surgery, and has no definitive cure. This study explored whether mitochondria-rich microvesicles (MVs) can be used to treat ED stemming from cavernous nerve injury (CNI) and investigated its potential mechanisms.Methods: We isolated MVs and mitochondria (MT) from PC12. The apoptosis rate, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial derived reactive oxygen species (mtROS), iron content, malondialdehyde (MDA) content and endogenous antioxidant system activity of corpus cavernosum smooth muscle cells (CCSMCs) cultured with MVs and MT were detected in vitro. In vivo, twenty-four male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI group were injected with PBS, MVs and MT respectively. After fourteen days of treatment, the erectile function was measured and penile tissues were collected for histological analysis. Subsequently, inhibition of mitochondria in MV was performed to explore the mechanism of the rescue experiment.Results: The CCSMCs, PC12-MVs and PC12-MT were successfully isolated and identified. After MVs culture, apoptosis rate, ROS, mtROS, iron content and MDA content of CCSMCs were significantly decreased, while MMP and the activities of endogenous antioxidant system were increased. MVs transplantation can significantly restore erectile function and smooth muscle content in CNIED rats. The rescue experiment suggested that MVs exerted the above therapeutic effect by transferring mitochondria within it.Conclusion: MVs transplantation significantly improve erectile function in CNI ED rats. MVs may play a role in anti-OS and anti-ferroptosis at the transplant site through efficient transfer of mitochondria, providing a potential treatment vehicle for CNI ED.Keywords: cavernous nerve injury, erectile dysfunction, microvesicles, oxidative stress, ferroptosis |
| format | Article |
| id | doaj-art-f6c19f2fc8e4410bb0cdb6ebcd9fa17e |
| institution | Kabale University |
| issn | 1178-2013 |
| language | English |
| publishDate | 2024-11-01 |
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| series | International Journal of Nanomedicine |
| spelling | doaj-art-f6c19f2fc8e4410bb0cdb6ebcd9fa17e2024-11-12T19:45:32ZengDove Medical PressInternational Journal of Nanomedicine1178-20132024-11-01Volume 19117451176597210Mitochondria-Rich Microvesicles Alleviate CNI ED by Transferring Mitochondria and Suppressing Local FerroptosisLiang ZChen ZZhang CChen CYang WZhang YWei HZhenkang Liang,* Zehong Chen,* Chaowei Zhang, Cui Chen, Wende Yang, Yuxuan Zhang, Hongbo Wei Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongbo Wei, Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road 600, Guangzhou, 510630, People’s Republic of China, Tel +86-020-85253000, Email weihb@mail.sysu.edu.cnPurpose: Erectile dysfunction (ED) frequently arises as a complication of pelvic surgeries, including rectal and prostate surgery, and has no definitive cure. This study explored whether mitochondria-rich microvesicles (MVs) can be used to treat ED stemming from cavernous nerve injury (CNI) and investigated its potential mechanisms.Methods: We isolated MVs and mitochondria (MT) from PC12. The apoptosis rate, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial derived reactive oxygen species (mtROS), iron content, malondialdehyde (MDA) content and endogenous antioxidant system activity of corpus cavernosum smooth muscle cells (CCSMCs) cultured with MVs and MT were detected in vitro. In vivo, twenty-four male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI group were injected with PBS, MVs and MT respectively. After fourteen days of treatment, the erectile function was measured and penile tissues were collected for histological analysis. Subsequently, inhibition of mitochondria in MV was performed to explore the mechanism of the rescue experiment.Results: The CCSMCs, PC12-MVs and PC12-MT were successfully isolated and identified. After MVs culture, apoptosis rate, ROS, mtROS, iron content and MDA content of CCSMCs were significantly decreased, while MMP and the activities of endogenous antioxidant system were increased. MVs transplantation can significantly restore erectile function and smooth muscle content in CNIED rats. The rescue experiment suggested that MVs exerted the above therapeutic effect by transferring mitochondria within it.Conclusion: MVs transplantation significantly improve erectile function in CNI ED rats. MVs may play a role in anti-OS and anti-ferroptosis at the transplant site through efficient transfer of mitochondria, providing a potential treatment vehicle for CNI ED.Keywords: cavernous nerve injury, erectile dysfunction, microvesicles, oxidative stress, ferroptosishttps://www.dovepress.com/mitochondria-rich-microvesicles-alleviate-cni-ed-by-transferring-mitoc-peer-reviewed-fulltext-article-IJNcavernous nerve injuryerectile dysfunctionmicrovesiclesoxidative stressferroptosis |
| spellingShingle | Liang Z Chen Z Zhang C Chen C Yang W Zhang Y Wei H Mitochondria-Rich Microvesicles Alleviate CNI ED by Transferring Mitochondria and Suppressing Local Ferroptosis International Journal of Nanomedicine cavernous nerve injury erectile dysfunction microvesicles oxidative stress ferroptosis |
| title | Mitochondria-Rich Microvesicles Alleviate CNI ED by Transferring Mitochondria and Suppressing Local Ferroptosis |
| title_full | Mitochondria-Rich Microvesicles Alleviate CNI ED by Transferring Mitochondria and Suppressing Local Ferroptosis |
| title_fullStr | Mitochondria-Rich Microvesicles Alleviate CNI ED by Transferring Mitochondria and Suppressing Local Ferroptosis |
| title_full_unstemmed | Mitochondria-Rich Microvesicles Alleviate CNI ED by Transferring Mitochondria and Suppressing Local Ferroptosis |
| title_short | Mitochondria-Rich Microvesicles Alleviate CNI ED by Transferring Mitochondria and Suppressing Local Ferroptosis |
| title_sort | mitochondria rich microvesicles alleviate cni ed by transferring mitochondria and suppressing local ferroptosis |
| topic | cavernous nerve injury erectile dysfunction microvesicles oxidative stress ferroptosis |
| url | https://www.dovepress.com/mitochondria-rich-microvesicles-alleviate-cni-ed-by-transferring-mitoc-peer-reviewed-fulltext-article-IJN |
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