1023 INVOLVEMENT OF RHO-KINASE/LIM-KINASE/COFILIN SIGNALING PATHWAY IN ERECTILE DYSFUNCTION AND CORPORAL FIBROSIS AFTER CAVERNOUS NERVE INJURY IN MALE RATS

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You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research (II)1 Apr 20131023 INVOLVEMENT OF RHO-KINASE/LIM-KINASE/COFILIN SIGNALING PATHWAY IN ERECTILE DYSFUNCTION AND CORPORAL FIBROSIS AFTER CAVERNOUS NERVE INJURY IN MALE RATS Min Chul Cho, Sang Hoon Song, Sung Yong Cho, Kwanjin Park, Soo Woong Kim, and Jae-Seung Paick Min Chul ChoMin Chul Cho Goyang, Korea, Republic of More articles by this author , Sang Hoon SongSang Hoon Song Seoul, Korea, Republic of More articles by this author , Sung Yong ChoSung Yong Cho Seoul, Korea, Republic of More articles by this author , Kwanjin ParkKwanjin Park Seoul, Korea, Republic of More articles by this author , Soo Woong KimSoo Woong Kim Seoul, Korea, Republic of More articles by this author , and Jae-Seung PaickJae-Seung Paick Seoul, Korea, Republic of More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.608AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Molecular mechanism of corporal fibrosis leading to erectile dysfunction (ED) after cavernous nerve (CN) injury is poorly understood. Recently, we demonstrated that sphingosine-1-phosphate/RhoA/ROCK1 pathway could be involved in corporal fibrosis after CN injury. Activation of ROCK1 is followed by activation of downstream target kinases, LIM-kinase2 (LIMK2) and cofilin, resulting in fibroblast-to-myofibroblast differentiation, a pathophysiologic feature of fibrosis. Thus, the aim of this study was to determine whether LIMK2/cofilin pathway, the downstream effector of ROCK1, was involved in ED and corporal fibrosis after CN injury in male rats. METHODS Forty eight 10-week-old male Sprague-Dawley rats were equally divided into 3 groups: sham surgery (S); bilateral CN crush injury (I); and bilateral CN resection (R). Within each of 3 groups, two subgroups were analyzed as a function of time (1 and 4 weeks postoperatively). At 1 and 4 weeks postoperatively, electrostimulation was performed to assess erectile function by maximal intracavernous pressure (ICP)/mean arterial pressure (MAP) ratio and areas under the curve (AUC). Western blot (ROCK1, phospho/total LIMK2, phospho/total cofilin), immunohistochemistry (α-SMA and phospho-LIMK2) and Masson's trichrome staining were performed. RESULTS At each time point, both I and R groups showed significantly lower ICP/MAP ratio and AUC than S group. Mean ICP/MAP and AUC showed a trend toward higher level in I group than R group, which was not significantly different. At all time points, I and R groups had a significantly decreased SM cell/collagen ratio and expression of α-SMA compared to the S group and a trend toward decreasing over the study period. On immunohistochemical staining, the LIMK2 expression in both I and R groups was significantly higher than that in S group at 1 week, but not at 4 weeks. Densitometry revealed a significantly higher expression of ROCK1 in I and R group compared to S group at 1 and 4 weeks. The ratio of phospho/total LIMK2 protein expression in I and R groups was significantly decreased at 1 week, but not significantly different from that in S group at 4 weeks. The ratio of phospho/total cofilin protein expression in R group significantly decreased starting from 1 week, while that in I group significantly decreased as late as 4 weeks. CONCLUSIONS Our data suggest that LIMK2/cofilin pathway can be involved in ED and corporal fibrosis associated with loss of SM after CN injury, and appears to be functional particularly in the early phase after CN injury. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e419-e420 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Min Chul Cho Goyang, Korea, Republic of More articles by this author Sang Hoon Song Seoul, Korea, Republic of More articles by this author Sung Yong Cho Seoul, Korea, Republic of More articles by this author Kwanjin Park Seoul, Korea, Republic of More articles by this author Soo Woong Kim Seoul, Korea, Republic of More articles by this author Jae-Seung Paick Seoul, Korea, Republic of More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...