Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury
We evaluated whether LIM-kinase 2 inhibitor (LIMK2i) could improve erectile function by suppressing corporal fibrosis through the normalization of the Rho-associated coiled-coil protein kinase 1 (ROCK1)/LIMK2/Cofilin pathway in a rat model of cavernous nerve crush injury (CNCI). Sixty 11-week-old ma...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2018-01-01
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| Series: | Asian Journal of Andrology |
| Subjects: | |
| Online Access: | http://www.ajandrology.com/article.asp?issn=1008-682X;year=2018;volume=20;issue=4;spage=372;epage=378;aulast=Park |
| _version_ | 1818024517673418752 |
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| author | Juhyun Park Sung Yong Cho Kwanjin Park Ji Sun Chai Hwancheol Son Soo Woong Kim Jae-Seung Paick Min Chul Cho |
| author_facet | Juhyun Park Sung Yong Cho Kwanjin Park Ji Sun Chai Hwancheol Son Soo Woong Kim Jae-Seung Paick Min Chul Cho |
| author_sort | Juhyun Park |
| collection | DOAJ |
| description | We evaluated whether LIM-kinase 2 inhibitor (LIMK2i) could improve erectile function by suppressing corporal fibrosis through the normalization of the Rho-associated coiled-coil protein kinase 1 (ROCK1)/LIMK2/Cofilin pathway in a rat model of cavernous nerve crush injury (CNCI). Sixty 11-week-old male Sprague-Dawley rats were divided equally into five groups: sham surgery (S), CNCI (I), and CNCI treated with low-dose (L), medium-dose (M), and high-dose (H) LIMK2i. The L, M, and H groups were treated with a daily intraperitoneal injection of LIMK2i (2.5, 5.0, and 10.0 mg kg−1 body weight, respectively) for 1 week after surgery. The erectile response was assessed using electrostimulation at 1 week, postoperatively. Penile tissues were processed for Masson's trichrome staining, double immunofluorescence, and Western blot assay. Erectile responses in the H group improved compared with the I group, while the M group showed only partial improvement. A significantly decreased smooth muscle/collagen ratio and an increased content of fibroblasts positive for phospho-LIMK2 were noted in the I group. The M and H groups revealed significant improvements in histological alterations and the dysregulated LIMK2/Cofilin pathway, except for LIMK2 phosphorylation in the M group. The inhibition of LIMK2 did not affect the ROCK1 protein expression. The content of fibroblasts positive for phospho-LIMK2 in the H group returned to the level found in the S group, whereas it did not in the M group. However, the L group did not exhibit such improvements. Our data suggest that the inhibition of LIMK2, particularly with administration of 10.0 mg kg−1 body weight LIMK2i, can improve corporal fibrosis and erectile function by normalizing the LIMK2/Cofilin pathway. |
| first_indexed | 2024-12-10T04:01:29Z |
| format | Article |
| id | doaj.art-bca059e41a5c4baa8594c839a1dc5847 |
| institution | Directory Open Access Journal |
| issn | 1008-682X 1745-7262 |
| language | English |
| last_indexed | 2024-12-10T04:01:29Z |
| publishDate | 2018-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Asian Journal of Andrology |
| spelling | doaj.art-bca059e41a5c4baa8594c839a1dc58472022-12-22T02:02:58ZengWolters Kluwer Medknow PublicationsAsian Journal of Andrology1008-682X1745-72622018-01-0120437237810.4103/aja.aja_82_17Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injuryJuhyun ParkSung Yong ChoKwanjin ParkJi Sun ChaiHwancheol SonSoo Woong KimJae-Seung PaickMin Chul ChoWe evaluated whether LIM-kinase 2 inhibitor (LIMK2i) could improve erectile function by suppressing corporal fibrosis through the normalization of the Rho-associated coiled-coil protein kinase 1 (ROCK1)/LIMK2/Cofilin pathway in a rat model of cavernous nerve crush injury (CNCI). Sixty 11-week-old male Sprague-Dawley rats were divided equally into five groups: sham surgery (S), CNCI (I), and CNCI treated with low-dose (L), medium-dose (M), and high-dose (H) LIMK2i. The L, M, and H groups were treated with a daily intraperitoneal injection of LIMK2i (2.5, 5.0, and 10.0 mg kg−1 body weight, respectively) for 1 week after surgery. The erectile response was assessed using electrostimulation at 1 week, postoperatively. Penile tissues were processed for Masson's trichrome staining, double immunofluorescence, and Western blot assay. Erectile responses in the H group improved compared with the I group, while the M group showed only partial improvement. A significantly decreased smooth muscle/collagen ratio and an increased content of fibroblasts positive for phospho-LIMK2 were noted in the I group. The M and H groups revealed significant improvements in histological alterations and the dysregulated LIMK2/Cofilin pathway, except for LIMK2 phosphorylation in the M group. The inhibition of LIMK2 did not affect the ROCK1 protein expression. The content of fibroblasts positive for phospho-LIMK2 in the H group returned to the level found in the S group, whereas it did not in the M group. However, the L group did not exhibit such improvements. Our data suggest that the inhibition of LIMK2, particularly with administration of 10.0 mg kg−1 body weight LIMK2i, can improve corporal fibrosis and erectile function by normalizing the LIMK2/Cofilin pathway.http://www.ajandrology.com/article.asp?issn=1008-682X;year=2018;volume=20;issue=4;spage=372;epage=378;aulast=Parkerectile dysfunction; fibrosis; LIM kinase; penis; prostatectomy |
| spellingShingle | Juhyun Park Sung Yong Cho Kwanjin Park Ji Sun Chai Hwancheol Son Soo Woong Kim Jae-Seung Paick Min Chul Cho Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury Asian Journal of Andrology erectile dysfunction; fibrosis; LIM kinase; penis; prostatectomy |
| title | Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury |
| title_full | Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury |
| title_fullStr | Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury |
| title_full_unstemmed | Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury |
| title_short | Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury |
| title_sort | role of inhibiting lim kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury |
| topic | erectile dysfunction; fibrosis; LIM kinase; penis; prostatectomy |
| url | http://www.ajandrology.com/article.asp?issn=1008-682X;year=2018;volume=20;issue=4;spage=372;epage=378;aulast=Park |
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