1112 INVOLVEMENT OF SPHINGOSINE-1-PHOSPHATE/RHOA/RHO-KINASE SIGNALING PATHWAY IN CORPORAL FIBROSIS FOLLOWING CAVERNOUS NERVE INJURY IN MALE RATS

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research1 Apr 20111112 INVOLVEMENT OF SPHINGOSINE-1-PHOSPHATE/RHOA/RHO-KINASE SIGNALING PATHWAY IN CORPORAL FIBROSIS FOLLOWING CAVERNOUS NERVE INJURY IN MALE RATS Min Chul Cho, Min Su Jeong, Kwanjin Park, Ji Sun Chai, Sun Hee Lee, Soo Woong Kim, Kwang Soo Lee, and Jae-Seung Paick Min Chul ChoMin Chul Cho Goyang, Korea, Republic of More articles by this author , Min Su JeongMin Su Jeong Seoul, Korea, Republic of More articles by this author , Kwanjin ParkKwanjin Park Seoul, Korea, Republic of More articles by this author , Ji Sun ChaiJi Sun Chai Seoul, Korea, Republic of More articles by this author , Sun Hee LeeSun Hee Lee Seoul, Korea, Republic of More articles by this author , Soo Woong KimSoo Woong Kim Seoul, Korea, Republic of More articles by this author , Kwang Soo LeeKwang Soo Lee Goyang, 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.2011.02.709AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Post-prostatectomy erectile dysfunction (ED) is thought to be due primarily to injury to cavernous nerve (CN) during surgery. Molecular mechanism of corporal fibrosis leading to ED after CN injury is poorly understood. RhoA/Rho-kinase (ROCK1) signaling pathway is a critical element in transforming growth factor-β (TGF-β)-induced vascular fibrosis. Sphingosine kinase 1 (Sphk1) stimulated by growth factor such as TGF-β1 increases sphingosine-1-phosphate (S1P), which leads to activation of RhoA via S1P type 2 receptor (S1P2) and RhoA exchange factor, resulting in fibroblast proliferation necessary for fibrosis. We hypothesized that TGF-β1 would activate SphK1 and the resulting S1P would lead to activation of RhoA/ROCK1 pathway via S1P2, leading to corporal fibrosis in a rat model of CN injury. The aim of this study was to determine whether TGF-β1, S1P and RhoA/ROCK1 pathways were involved in corporal fibrosis after bilateral CN injury in rats. METHODS Forty eight 10-week-old male Sprague-Dawley rats were equally divided into 4 groups: normal control (C); sham surgery (S); bilateral CN crush injury (I); and bilateral CN transection (T). Within each of 4 groups, two subgroups were analyzed as a function of time (1 and 8 weeks postoperatively). Penile tissue was processed for immunoblot (RhoA, ROCK1, phospho-MYPT1), RT-PCR (TGF-β1, SphK1, and S1P2), immunohistochemistry (α-SMA), and Masson′s trichrome staining. RESULTS At 1 and 8 weeks postoperatively, I and T groups had a significantly decreased SMC/collagen ratio, expression of α-SMA and phopho-MYPT1 compared to C group. Densitometry revealed a significantly higher expression of RhoA and ROCK1 in T group compared to C group at 1 and 8 weeks postoperatively. For I group, expression of RhoA significantly increased starting from 1 week postoperatively, but expression of ROCK1 significantly increased as late as 8 weeks following injury. Expression of TGF-β1 and S1P2 mRNA in I or T group remained significantly increased up to 8 weeks compared to C group, despite significant reduction at 8 weeks compared to 1 week postoperatively. Expression of SphK1 mRNA in I and T groups was significantly increased at 1 week, but decreased by 8 weeks after CN injury, and was not signicantly different from C group. CONCLUSIONS The present study suggests that S1P/RhoA/ROCK1 signaling pathway may be involved in corporal fibrosis associated with loss of smooth muscle through coordination with TGF-β1 after CN injury, and appears to be functional particularly in the early phase after CN injury. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e447 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Min Chul Cho Goyang, Korea, Republic of More articles by this author Min Su Jeong Seoul, Korea, Republic of More articles by this author Kwanjin Park Seoul, Korea, Republic of More articles by this author Ji Sun Chai Seoul, Korea, Republic of More articles by this author Sun Hee Lee Seoul, Korea, Republic of More articles by this author Soo Woong Kim Seoul, Korea, Republic of More articles by this author Kwang Soo Lee Goyang, 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 ...