miR-145-enriched BMSCs-derived exosomes ameliorate neurogenic erectile dysfunction in aged rats via TGFBR2 inhibition
Background: Neurogenic erectile dysfunction (ED) is a prevalent complication following radical prostatectomy in elderly patients, primarily resulting from the apoptosis of corpus cavernosum smooth muscle cells (CCSMCs) and the subsequent excessive fibrosis of the corpus cavernosum. Aim: This study a...
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Elsevier
2025-06-01
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| Series: | Regenerative Therapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S235232042500080X |
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| author | Yude Hong Zejia Feng Yunlong Ge Yuhang Xi Bowen Zhang Jianjie Wu Tian Xia Bowen Tang Wei Wang Jun Chen Hua Wang Hengjun Xiao |
| author_facet | Yude Hong Zejia Feng Yunlong Ge Yuhang Xi Bowen Zhang Jianjie Wu Tian Xia Bowen Tang Wei Wang Jun Chen Hua Wang Hengjun Xiao |
| author_sort | Yude Hong |
| collection | DOAJ |
| description | Background: Neurogenic erectile dysfunction (ED) is a prevalent complication following radical prostatectomy in elderly patients, primarily resulting from the apoptosis of corpus cavernosum smooth muscle cells (CCSMCs) and the subsequent excessive fibrosis of the corpus cavernosum. Aim: This study aimed to compare the therapeutic effects of exosomes derived from lentivirus-transfected miR-145 bone marrow mesenchymal stem cells (Exo-145) and unmodified BMSCs-derived exosomes (Exo) in aged rats with bilateral cavernous nerve injury (BCNI) and investigate the underlying mechanisms. Methods: Twenty-four-month-old male rats were assigned to four groups, namely Sham, BCNI, Exo, and Exo-145. Three weeks after treatment, erectile function was assessed by measuring the maximal intracavernosal pressure to mean arterial pressure (ICP/MAP) ratio. Apoptosis and fibrosis were semi-quantitatively analyzed using TUNEL and Masson's trichrome staining, respectively. In vitro, CCSMCs were subjected to H2O2-induced oxidative stress, and the protective effects of Exo-145 were evaluated through flow cytometry and Western blot. Lastly, the targets and mechanisms of miR-145 were further validated using dual-luciferase reporter assays and rescue experiments. Results: Exo-145 significantly outperformed Exo in restoring erectile function in aged BCNI rats, as evidenced by the significantly higher maximal ICP/MAP ratio, a marked reduction in TUNEL-positive cell count, and marked suppression of fibrosis in cavernous tissue. Moreover, Masson's trichrome staining displayed a substantial decrease in collagen deposition. In vitro, Exo-145 alleviated H2O2-induced apoptosis in CCSMCs by downregulating Cleaved Caspase-3 expression and Bax while concurrently upregulating Bcl-2 expression. TGFBR2 was identified as a direct target of miR-145 through dual-luciferase reporter assays, with its overexpression partially reversing the protective effects of Exo-145. Conclusion: Exo-145 demonstrates superior efficacy compared to Exo in treating aged neurogenic ED by targeting TGFBR2 to alleviate apoptosis and fibrosis. It may represent a promising cell-free therapeutic option for neurogenic erectile dysfunction in elderly patients and could offer new perspectives for improving their prognosis. |
| format | Article |
| id | doaj-art-958964fec40a42bcbed2f9cd2acbd7c3 |
| institution | OA Journals |
| issn | 2352-3204 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj-art-958964fec40a42bcbed2f9cd2acbd7c32025-08-20T01:51:14ZengElsevierRegenerative Therapy2352-32042025-06-012945546510.1016/j.reth.2025.04.004miR-145-enriched BMSCs-derived exosomes ameliorate neurogenic erectile dysfunction in aged rats via TGFBR2 inhibitionYude Hong0Zejia Feng1Yunlong Ge2Yuhang Xi3Bowen Zhang4Jianjie Wu5Tian Xia6Bowen Tang7Wei Wang8Jun Chen9Hua Wang10Hengjun Xiao11Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Department of Urology, The Second Affiliated Hospital, University of South China, Hengyang, ChinaDepartment of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Infertility and Sexual Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Infertility and Sexual Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Infertility and Sexual Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Corresponding authors.Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Corresponding authors.Background: Neurogenic erectile dysfunction (ED) is a prevalent complication following radical prostatectomy in elderly patients, primarily resulting from the apoptosis of corpus cavernosum smooth muscle cells (CCSMCs) and the subsequent excessive fibrosis of the corpus cavernosum. Aim: This study aimed to compare the therapeutic effects of exosomes derived from lentivirus-transfected miR-145 bone marrow mesenchymal stem cells (Exo-145) and unmodified BMSCs-derived exosomes (Exo) in aged rats with bilateral cavernous nerve injury (BCNI) and investigate the underlying mechanisms. Methods: Twenty-four-month-old male rats were assigned to four groups, namely Sham, BCNI, Exo, and Exo-145. Three weeks after treatment, erectile function was assessed by measuring the maximal intracavernosal pressure to mean arterial pressure (ICP/MAP) ratio. Apoptosis and fibrosis were semi-quantitatively analyzed using TUNEL and Masson's trichrome staining, respectively. In vitro, CCSMCs were subjected to H2O2-induced oxidative stress, and the protective effects of Exo-145 were evaluated through flow cytometry and Western blot. Lastly, the targets and mechanisms of miR-145 were further validated using dual-luciferase reporter assays and rescue experiments. Results: Exo-145 significantly outperformed Exo in restoring erectile function in aged BCNI rats, as evidenced by the significantly higher maximal ICP/MAP ratio, a marked reduction in TUNEL-positive cell count, and marked suppression of fibrosis in cavernous tissue. Moreover, Masson's trichrome staining displayed a substantial decrease in collagen deposition. In vitro, Exo-145 alleviated H2O2-induced apoptosis in CCSMCs by downregulating Cleaved Caspase-3 expression and Bax while concurrently upregulating Bcl-2 expression. TGFBR2 was identified as a direct target of miR-145 through dual-luciferase reporter assays, with its overexpression partially reversing the protective effects of Exo-145. Conclusion: Exo-145 demonstrates superior efficacy compared to Exo in treating aged neurogenic ED by targeting TGFBR2 to alleviate apoptosis and fibrosis. It may represent a promising cell-free therapeutic option for neurogenic erectile dysfunction in elderly patients and could offer new perspectives for improving their prognosis.http://www.sciencedirect.com/science/article/pii/S235232042500080XErectile dysfunctionExosomesmiR-145TGFBR2Cavernous nerve injury |
| spellingShingle | Yude Hong Zejia Feng Yunlong Ge Yuhang Xi Bowen Zhang Jianjie Wu Tian Xia Bowen Tang Wei Wang Jun Chen Hua Wang Hengjun Xiao miR-145-enriched BMSCs-derived exosomes ameliorate neurogenic erectile dysfunction in aged rats via TGFBR2 inhibition Regenerative Therapy Erectile dysfunction Exosomes miR-145 TGFBR2 Cavernous nerve injury |
| title | miR-145-enriched BMSCs-derived exosomes ameliorate neurogenic erectile dysfunction in aged rats via TGFBR2 inhibition |
| title_full | miR-145-enriched BMSCs-derived exosomes ameliorate neurogenic erectile dysfunction in aged rats via TGFBR2 inhibition |
| title_fullStr | miR-145-enriched BMSCs-derived exosomes ameliorate neurogenic erectile dysfunction in aged rats via TGFBR2 inhibition |
| title_full_unstemmed | miR-145-enriched BMSCs-derived exosomes ameliorate neurogenic erectile dysfunction in aged rats via TGFBR2 inhibition |
| title_short | miR-145-enriched BMSCs-derived exosomes ameliorate neurogenic erectile dysfunction in aged rats via TGFBR2 inhibition |
| title_sort | mir 145 enriched bmscs derived exosomes ameliorate neurogenic erectile dysfunction in aged rats via tgfbr2 inhibition |
| topic | Erectile dysfunction Exosomes miR-145 TGFBR2 Cavernous nerve injury |
| url | http://www.sciencedirect.com/science/article/pii/S235232042500080X |
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