Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury

作     者：Juhyun Park Sung Yong Cho Kwanjin Park Ji Sun Chai Hwancheol Son Soo Woong Kim Jae-Seung Paick Min Chul Cho 

作者机构：Department of Urology Seoul National University College of Medicine SMG-SNU Boramae Medical Center Seoul 03080 Korea Department of Urology Seoul Nationa University College of Medicine Seoul National University Hospital Seoul 07061 Korea 

出 版 物：《Asian Journal of Andrology》 (亚洲男性学杂志（英文版）)

年 卷 期：2018年第20卷第4期

页      面：372-378页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 1002[医学-临床医学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 071002[理学-动物学] 

基　　金：supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science  ICT and Future Planning 

主　　题：erectile dysfunction fibrosis LIM kinase penis prostatectomy 

摘      要：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 （CNCl）. Sixty 11-week-old male Sprague-Dawley rats were divided equally into five groups： sham surgery （S）, CNCl （I）, and CNCl 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-/IMK2 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.