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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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
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| Series: | Regenerative Therapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S235232042500080X |
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| Summary: | 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. |
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| ISSN: | 2352-3204 |