hUC-MSC preserves erectile function by restoring mitochondrial mass of penile smooth muscle cells in a rat model of cavernous nerve injury via SIRT1/PGC-1a/TFAM signaling
Abstract Background Cavernous nerve injury-induced erectile dysfunction (CNI-ED) is a common complication following radical prostatectomy and severely affects patients’ quality of life. The mitochondrial impairment in corpus cavernosum smooth muscle cells (CCSMCs) may be an important pathological me...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s40659-024-00578-y |
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| author | Mengbo Yang Xinda Chen Ming Zhang Xiaolin Zhang Dongdong Xiao Huiming Xu Mujun Lu |
| author_facet | Mengbo Yang Xinda Chen Ming Zhang Xiaolin Zhang Dongdong Xiao Huiming Xu Mujun Lu |
| author_sort | Mengbo Yang |
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| description | Abstract Background Cavernous nerve injury-induced erectile dysfunction (CNI-ED) is a common complication following radical prostatectomy and severely affects patients’ quality of life. The mitochondrial impairment in corpus cavernosum smooth muscle cells (CCSMCs) may be an important pathological mechanism of CNI-ED. Previous studies have shown that transplantation of human adipose derived stem cells (ADSC) can alleviate CNI-ED in a rat model. However, little is known about the effect of human umbilical cord mesenchymal stem cells (hUC-MSC) on CNI-ED. It remains unclear whether hUC-MSC can ameliorate mitochondrial damage in CCSMCs. In this study, we aimed to investigate the impacts of hUC-MSC on the mitochondrial mass and function of CCSMCs, as well as elucidate its underlying molecular mechanism. Methods The CNI-ED rat model was established by bilaterally crushing cavernous nerves. Subsequently, hUC-MSC were transplanted into the cavernosum and ADSC were injected as a positive control group. Erectile function evaluation and histological detection were performed 4 weeks after cell transplantation. In vitro, CCSMCs underwent hypoxia and were then co-cultured with ADSC or hUC-MSC using a transwell system. The mitochondrial mass and function, as well as signaling pathways, were investigated. To explore the role of the SIRT1/PGC-1α/TFAM pathway in regulating mitochondrial biogenesis of CCSMCs, we knocked down SIRT1 by siRNA. Results The administration of hUC-MSC significantly improved erectile function of CNI-ED rats and reduced the ratio of collagen to smooth muscle. Specifically, hUC-MSC treatment restored mitochondrial mass and function in CCSMCs injured by CNI or hypoxia, and inhibited the apoptosis of CCSMCs. Mechanistically, the application of hUC-MSC activated SIRT1/PGC-1α/TFAM pathway both in rat penile tissues and CCSMCs. In addition, knockdown of SIRT1 in CCSMCs abolished the protective effects of hUC-MSC on mitochondrial mass and function, while leading to an increase in cellular apoptosis. Conclusions hUC-MSC contribute to the recovery of erectile function in CNI-ED rats by restoring mitochondrial mass and function of CCSMCs through the SIRT1/PGC-1α/TFAM pathway. Our present study offers new insights into the role and molecular mechanisms of hUC-MSC in regulating mitochondrial homeostasis, thereby facilitating the restoration of the erectile function in CNI-ED. |
| format | Article |
| id | doaj-art-1feb553c43354144927653a0c7cad420 |
| institution | Kabale University |
| issn | 0717-6287 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-1feb553c43354144927653a0c7cad4202025-02-02T12:09:33ZengBMCBiological Research0717-62872025-01-0158111610.1186/s40659-024-00578-yhUC-MSC preserves erectile function by restoring mitochondrial mass of penile smooth muscle cells in a rat model of cavernous nerve injury via SIRT1/PGC-1a/TFAM signalingMengbo Yang0Xinda Chen1Ming Zhang2Xiaolin Zhang3Dongdong Xiao4Huiming Xu5Mujun Lu6Department of Urology and Andrology, Renji Hospital, Shanghai Institute of Andrology, School of Medicine, Shanghai Jiaotong UniversityDepartment of Urology and Andrology, Renji Hospital, Shanghai Institute of Andrology, School of Medicine, Shanghai Jiaotong UniversityDepartment of Urology and Andrology, Renji Hospital, Shanghai Institute of Andrology, School of Medicine, Shanghai Jiaotong UniversityDepartment of Urology and Andrology, Renji Hospital, Shanghai Institute of Andrology, School of Medicine, Shanghai Jiaotong UniversityDepartment of Urology and Andrology, Renji Hospital, Shanghai Institute of Andrology, School of Medicine, Shanghai Jiaotong UniversityState Laboratory of Systems Medicine for Cancer, Renji-MedX Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Urology and Andrology, Renji Hospital, Shanghai Institute of Andrology, School of Medicine, Shanghai Jiaotong UniversityAbstract Background Cavernous nerve injury-induced erectile dysfunction (CNI-ED) is a common complication following radical prostatectomy and severely affects patients’ quality of life. The mitochondrial impairment in corpus cavernosum smooth muscle cells (CCSMCs) may be an important pathological mechanism of CNI-ED. Previous studies have shown that transplantation of human adipose derived stem cells (ADSC) can alleviate CNI-ED in a rat model. However, little is known about the effect of human umbilical cord mesenchymal stem cells (hUC-MSC) on CNI-ED. It remains unclear whether hUC-MSC can ameliorate mitochondrial damage in CCSMCs. In this study, we aimed to investigate the impacts of hUC-MSC on the mitochondrial mass and function of CCSMCs, as well as elucidate its underlying molecular mechanism. Methods The CNI-ED rat model was established by bilaterally crushing cavernous nerves. Subsequently, hUC-MSC were transplanted into the cavernosum and ADSC were injected as a positive control group. Erectile function evaluation and histological detection were performed 4 weeks after cell transplantation. In vitro, CCSMCs underwent hypoxia and were then co-cultured with ADSC or hUC-MSC using a transwell system. The mitochondrial mass and function, as well as signaling pathways, were investigated. To explore the role of the SIRT1/PGC-1α/TFAM pathway in regulating mitochondrial biogenesis of CCSMCs, we knocked down SIRT1 by siRNA. Results The administration of hUC-MSC significantly improved erectile function of CNI-ED rats and reduced the ratio of collagen to smooth muscle. Specifically, hUC-MSC treatment restored mitochondrial mass and function in CCSMCs injured by CNI or hypoxia, and inhibited the apoptosis of CCSMCs. Mechanistically, the application of hUC-MSC activated SIRT1/PGC-1α/TFAM pathway both in rat penile tissues and CCSMCs. In addition, knockdown of SIRT1 in CCSMCs abolished the protective effects of hUC-MSC on mitochondrial mass and function, while leading to an increase in cellular apoptosis. Conclusions hUC-MSC contribute to the recovery of erectile function in CNI-ED rats by restoring mitochondrial mass and function of CCSMCs through the SIRT1/PGC-1α/TFAM pathway. Our present study offers new insights into the role and molecular mechanisms of hUC-MSC in regulating mitochondrial homeostasis, thereby facilitating the restoration of the erectile function in CNI-ED.https://doi.org/10.1186/s40659-024-00578-yCavernous nerve injury-induced erectile dysfunctionCorpus cavernous smooth muscle cellMesenchymal stem cellSIRT1/PGC-1α/TFAM pathway |
| spellingShingle | Mengbo Yang Xinda Chen Ming Zhang Xiaolin Zhang Dongdong Xiao Huiming Xu Mujun Lu hUC-MSC preserves erectile function by restoring mitochondrial mass of penile smooth muscle cells in a rat model of cavernous nerve injury via SIRT1/PGC-1a/TFAM signaling Biological Research Cavernous nerve injury-induced erectile dysfunction Corpus cavernous smooth muscle cell Mesenchymal stem cell SIRT1/PGC-1α/TFAM pathway |
| title | hUC-MSC preserves erectile function by restoring mitochondrial mass of penile smooth muscle cells in a rat model of cavernous nerve injury via SIRT1/PGC-1a/TFAM signaling |
| title_full | hUC-MSC preserves erectile function by restoring mitochondrial mass of penile smooth muscle cells in a rat model of cavernous nerve injury via SIRT1/PGC-1a/TFAM signaling |
| title_fullStr | hUC-MSC preserves erectile function by restoring mitochondrial mass of penile smooth muscle cells in a rat model of cavernous nerve injury via SIRT1/PGC-1a/TFAM signaling |
| title_full_unstemmed | hUC-MSC preserves erectile function by restoring mitochondrial mass of penile smooth muscle cells in a rat model of cavernous nerve injury via SIRT1/PGC-1a/TFAM signaling |
| title_short | hUC-MSC preserves erectile function by restoring mitochondrial mass of penile smooth muscle cells in a rat model of cavernous nerve injury via SIRT1/PGC-1a/TFAM signaling |
| title_sort | huc msc preserves erectile function by restoring mitochondrial mass of penile smooth muscle cells in a rat model of cavernous nerve injury via sirt1 pgc 1a tfam signaling |
| topic | Cavernous nerve injury-induced erectile dysfunction Corpus cavernous smooth muscle cell Mesenchymal stem cell SIRT1/PGC-1α/TFAM pathway |
| url | https://doi.org/10.1186/s40659-024-00578-y |
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