Ablation of IGFBP5 expression alleviates neurogenic erectile dysfunction by inducing neurovascular regeneration
"Purpose: To investigate the therapeutic potential of eliminating insulin-like growth factor-binding protein 5 (IGFBP5) expression in improving erectile function in mice with cavernous nerve injury (CNI)-induced erectile dysfunction (ED). Materials and Methods: Eight-week-old male C57BL/6 mice...
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| Format: | Article |
| Language: | English |
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Korean Urological Association
2025-01-01
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| Series: | Investigative and Clinical Urology |
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| Online Access: | https://www.icurology.org/pdf/10.4111/icu.20240325 |
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| author | Jiyeon Ock Guo Nan Yin Fang-Yuan Liu Yan Huang Fitri Rahma Fridayana Minh Nhat Vo Ji-Kan Ryu |
| author_facet | Jiyeon Ock Guo Nan Yin Fang-Yuan Liu Yan Huang Fitri Rahma Fridayana Minh Nhat Vo Ji-Kan Ryu |
| author_sort | Jiyeon Ock |
| collection | DOAJ |
| description | "Purpose: To investigate the therapeutic potential of eliminating insulin-like growth factor-binding protein 5 (IGFBP5) expression in improving erectile function in mice with cavernous nerve injury (CNI)-induced erectile dysfunction (ED).
Materials and Methods: Eight-week-old male C57BL/6 mice were divided into four groups: a sham-operated group and three CNI-induced ED groups. The CNI-induced ED groups were treated with intracavernous injections 3 days before the CNI procedure. These injections included phosphate-buffered saline, scrambled control short hairpin RNA (shRNA), or shRNA targeting mouse IGFBP5 lentiviral particles. One week after CNI, erectile function was evaluated and the penile tissue was then harvested for histological examination and western blot analysis. Additionally, the major pelvic ganglia (MPG) and dorsal root ganglia (DRG) were cultured for ex vivo neurite outgrowth assays.
Results: Following CNI, IGFBP5 expression in the cavernous tissues significantly increased, reaching its peak at day 7. First, ablation of IGFBP5 expression promotes neurite sprouting in MPG and DRG when exposed to lipopolysaccharide. Second, ablating IGFBP5 expression in CNI-induced ED mice improved erectile function, likely owing to increased neurovascular contents, including endothelial cells, pericytes, and neuronal processes. Third, ablating IGFBP5 expression in CNI-induced ED mice promoted neurovascular regeneration by increasing cell proliferation, reducing apoptosis, and decreasing Reactive oxygen species production. Finally, western blot analysis demonstrated that IGFBP5 ablation attenuated the JNK/c-Jun signaling pathway, activated the PI3K/AKT signaling pathway, and increased vascular endothelial growth factor and neurotrophic factor expression.
Conclusions: Ablating IGFBP5 expression enhanced neurovascular regeneration and ultimately improved erectile function in CNI-induced ED mice."
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| format | Article |
| id | doaj-art-f2105d8a9634470e9935062b9fe7e0ee |
| institution | Kabale University |
| issn | 2466-0493 2466-054X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Korean Urological Association |
| record_format | Article |
| series | Investigative and Clinical Urology |
| spelling | doaj-art-f2105d8a9634470e9935062b9fe7e0ee2025-01-09T09:23:57ZengKorean Urological AssociationInvestigative and Clinical Urology2466-04932466-054X2025-01-01661748610.4111/icu.20240325Ablation of IGFBP5 expression alleviates neurogenic erectile dysfunction by inducing neurovascular regenerationJiyeon Ock0https://orcid.org/0000-0002-8264-4939Guo Nan Yin1https://orcid.org/0000-0002-2512-7337Fang-Yuan Liu2https://orcid.org/0000-0001-7218-6607 Yan Huang3https://orcid.org/0000-0001-7815-5772 Fitri Rahma Fridayana4https://orcid.org/0000-0002-1478-6492Minh Nhat Vo5https://orcid.org/0000-0002-8669-559XJi-Kan Ryu6https://orcid.org/0000-0003-0025-6025National Research Center for Sexual Medicine and Department of Urology, Inha University College of Medicine, Incheon, Korea.National Research Center for Sexual Medicine and Department of Urology, Inha University College of Medicine, Incheon, Korea.National Research Center for Sexual Medicine and Department of Urology, Inha University College of Medicine, Incheon, Korea.National Research Center for Sexual Medicine and Department of Urology, Inha University College of Medicine, Incheon, Korea.National Research Center for Sexual Medicine and Department of Urology, Inha University College of Medicine, Incheon, Korea.National Research Center for Sexual Medicine and Department of Urology, Inha University College of Medicine, Incheon, Korea.National Research Center for Sexual Medicine and Department of Urology, Inha University College of Medicine, Incheon, Korea."Purpose: To investigate the therapeutic potential of eliminating insulin-like growth factor-binding protein 5 (IGFBP5) expression in improving erectile function in mice with cavernous nerve injury (CNI)-induced erectile dysfunction (ED). Materials and Methods: Eight-week-old male C57BL/6 mice were divided into four groups: a sham-operated group and three CNI-induced ED groups. The CNI-induced ED groups were treated with intracavernous injections 3 days before the CNI procedure. These injections included phosphate-buffered saline, scrambled control short hairpin RNA (shRNA), or shRNA targeting mouse IGFBP5 lentiviral particles. One week after CNI, erectile function was evaluated and the penile tissue was then harvested for histological examination and western blot analysis. Additionally, the major pelvic ganglia (MPG) and dorsal root ganglia (DRG) were cultured for ex vivo neurite outgrowth assays. Results: Following CNI, IGFBP5 expression in the cavernous tissues significantly increased, reaching its peak at day 7. First, ablation of IGFBP5 expression promotes neurite sprouting in MPG and DRG when exposed to lipopolysaccharide. Second, ablating IGFBP5 expression in CNI-induced ED mice improved erectile function, likely owing to increased neurovascular contents, including endothelial cells, pericytes, and neuronal processes. Third, ablating IGFBP5 expression in CNI-induced ED mice promoted neurovascular regeneration by increasing cell proliferation, reducing apoptosis, and decreasing Reactive oxygen species production. Finally, western blot analysis demonstrated that IGFBP5 ablation attenuated the JNK/c-Jun signaling pathway, activated the PI3K/AKT signaling pathway, and increased vascular endothelial growth factor and neurotrophic factor expression. Conclusions: Ablating IGFBP5 expression enhanced neurovascular regeneration and ultimately improved erectile function in CNI-induced ED mice." https://www.icurology.org/pdf/10.4111/icu.20240325apoptosiserectile dysfunctioninsulin-like growth factor binding protein 5nerve regenerationreactive oxygen species |
| spellingShingle | Jiyeon Ock Guo Nan Yin Fang-Yuan Liu Yan Huang Fitri Rahma Fridayana Minh Nhat Vo Ji-Kan Ryu Ablation of IGFBP5 expression alleviates neurogenic erectile dysfunction by inducing neurovascular regeneration Investigative and Clinical Urology apoptosis erectile dysfunction insulin-like growth factor binding protein 5 nerve regeneration reactive oxygen species |
| title | Ablation of IGFBP5 expression alleviates neurogenic erectile dysfunction by inducing neurovascular regeneration |
| title_full | Ablation of IGFBP5 expression alleviates neurogenic erectile dysfunction by inducing neurovascular regeneration |
| title_fullStr | Ablation of IGFBP5 expression alleviates neurogenic erectile dysfunction by inducing neurovascular regeneration |
| title_full_unstemmed | Ablation of IGFBP5 expression alleviates neurogenic erectile dysfunction by inducing neurovascular regeneration |
| title_short | Ablation of IGFBP5 expression alleviates neurogenic erectile dysfunction by inducing neurovascular regeneration |
| title_sort | ablation of igfbp5 expression alleviates neurogenic erectile dysfunction by inducing neurovascular regeneration |
| topic | apoptosis erectile dysfunction insulin-like growth factor binding protein 5 nerve regeneration reactive oxygen species |
| url | https://www.icurology.org/pdf/10.4111/icu.20240325 |
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