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Restoring erectile function by combined treatment with JNK inhibitor and HDAC inhibitor in a rat model of cavernous nerve injury
DC Field | Value | Language |
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dc.contributor.author | Lee, Junghoon | - |
dc.contributor.author | Cho, Min Chul | - |
dc.contributor.author | Son, Hwancheol | - |
dc.contributor.author | Kim, Soo Woong | - |
dc.date.accessioned | 2022-06-22T00:06:12Z | - |
dc.date.available | 2022-06-22T00:06:12Z | - |
dc.date.created | 2022-05-12 | - |
dc.date.issued | 2022-05 | - |
dc.identifier.citation | Andrology, Vol.10 No.4, pp.758-766 | - |
dc.identifier.issn | 2047-2927 | - |
dc.identifier.uri | https://hdl.handle.net/10371/182703 | - |
dc.description.abstract | © 2022 American Society of Andrology and European Academy of AndrologyBackground: The main pathophysiologic conditions of erectile dysfunction (ED) after radical prostatectomy are considered to be corporal fibrosis and apoptosis induced by cavernosal nerve (CN) injury. Objectives: In a rat model of CN crush injury (CNCI), we investigated whether combination treatment with JNK inhibitor (JNKi), SP600125, and HDAC inhibitor (HDACi), suberoylanilide-hydroxamic-7 acid (SAHA), for 2 weeks after CNCI would restore erectile function by suppressing fibrosis and apoptosis through normalization of JNK and HDAC pathways. Materials and methods: Seventy 12-week-old rats were randomly divided into five groups: Sham surgery, CNCI alone, CNCI treated with daily intraperitoneal injection of 10 mg/kg JNKi, CNCI treated with daily oral administration of 25.0 mg/kg HDACi, and CNCI daily treated with a combination. Two weeks after CNCI, we investigated the erectile response to electrostimulation and conducted histological staining, caspase-3 activity assay, and western blot analysis. Results: CNCI alone resulted in significantly reduced intracavernosal pressure/mean arterial pressure (MAP) and area under the curve/MAP, decreased smooth muscle (SM)/collagen ratio and SM content, higher caspase-3 activity, and increased protein levels of total HDAC3, transforming growth factor (TGF)-β, fibronectin, and c-Jun phosphorylation, compared with the Sham surgery. The CNCI groups exposed to JNKi, HDACi or both showed improvements in erectile-responses and SM/collagen ratio, compared to the CNCI alone. The combined treatment showed additional improvement in erectile responses at 1.0V stimulation and in SM/collagen ratio compared to the single agent treatment. SM content, caspase-3 activity, and c-Jun phosphorylation improved in the two CNCI groups exposed to JNKi. The two CNCI groups exposed to HDACi showed normalization of protein levels of HDAC3, fibronectin, and TGF-β. Discussion and conclusions: The combined administration of JNKi and HDACi during the acute phase after CNCI in rats can preserve ED by suppressing cavernosal fibrosis and apoptosis by normalizing the HDAC/TGF-β and JNK pathways. | - |
dc.language | 영어 | - |
dc.publisher | John Wiley and Sons Inc. | - |
dc.title | Restoring erectile function by combined treatment with JNK inhibitor and HDAC inhibitor in a rat model of cavernous nerve injury | - |
dc.type | Article | - |
dc.identifier.doi | 10.1111/andr.13154 | - |
dc.citation.journaltitle | Andrology | - |
dc.identifier.wosid | 000749551100001 | - |
dc.identifier.scopusid | 2-s2.0-85124107036 | - |
dc.citation.endpage | 766 | - |
dc.citation.number | 4 | - |
dc.citation.startpage | 758 | - |
dc.citation.volume | 10 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Son, Hwancheol | - |
dc.contributor.affiliatedAuthor | Kim, Soo Woong | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
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