MP81-14 HUMAN TISSUE KALLIKREIN 1 AMELIORATES ERECTILE FUNCTION VIA MODULATING AUTOPHAGY AND ACTIVATING HIF-1?/COX-2 PATHWAY IN AGED TRANSGENIC RATS

Abstract

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology II1 Apr 2017MP81-14 HUMAN TISSUE KALLIKREIN 1 AMELIORATES ERECTILE FUNCTION VIA MODULATING AUTOPHAGY AND ACTIVATING HIF-1?/COX-2 PATHWAY IN AGED TRANSGENIC RATS Zhe Tang, Kai Cui, Yang Luan, Yajun Ruan, Tao Wang, Jun Yang, Shaogang Wang, and Jihong Liu Zhe TangZhe Tang More articles by this author , Kai CuiKai Cui More articles by this author , Yang LuanYang Luan More articles by this author , Yajun RuanYajun Ruan More articles by this author , Tao WangTao Wang More articles by this author , Jun YangJun Yang More articles by this author , Shaogang WangShaogang Wang More articles by this author , and Jihong LiuJihong Liu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2540AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Our previous studies have demonstrated that Human Tissue Kallikrein 1 (hKLK1) improved erectile function via several signaling pathways related to such as oxidative stress or corporal cavernosal fibrosis. However, the potential molecular mechanisms of hKLK1 inhibited age-related erectile dysfunction via modulating autophagy remains unknown. The aim of this article is to partly clarify the mechanisms of hKLK1 improving the erectile function in aged rats. METHODS Male wild-type Sprague-Dawley rats (WTR) and transgenic rats expressing the hKLK1 gene (TGR) were fed to 4 and 18 months of age, respectively, and divided into three groups: young WTR (yWTR) as the control, aged WTR (aWTR) and aged TGR (aTGR). Cavernous nerve electrostimulation was used to evaluate the erectile function of all rats. Transmission electron microscopy, immunohistochemistry, and western blotting were performed to determine the levels of autophagy. Related signaling pathways were detected by western blot and immunohistochemistry. RESULTS Compared with the yWTR group and aTGR group, the aWTR group showed (1)lower erectile function: lower intracavernosal pressure(ICP)/mean arterial pressure(MAP) ratio; (2) reduced expressions of eNOS and nNOS, lower NO level; (3) inhibited autophagy: decreased autophagosomes, lower expressions of BECN1 and LC3-II; and (4) low expression levels of PI3K/Akt/mTOR and Hif-1a/Cox-2 pathways. CONCLUSIONS The hKLK1 gene played a potential role of restoring erectile function in aged transgenic rats through modulating autophagy via PI3K/Akt/mTOR and Hif-1a/Cox-2 pathways. This finding provided evidence for hKLK1 being gene therapy method of age-related erectile dysfunction. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1094 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Zhe Tang More articles by this author Kai Cui More articles by this author Yang Luan More articles by this author Yajun Ruan More articles by this author Tao Wang More articles by this author Jun Yang More articles by this author Shaogang Wang More articles by this author Jihong Liu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...