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• W2796236462 abstract "You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology I1 Apr 2018MP43-07 INTRACAVERNOSAL ADENO-ASSOCIATED VIRUS MEDIATED S100A1 GENE TRANSFER ENHANCES ERECTILE FUNCTION IN DIABETIC RATS Zhe Yu, Yan Zhang, Jun Yang, Zhe Tang, Tao Wang, Jihong Liu, and Shaogang Wang Zhe YuZhe Yu More articles by this author , Yan ZhangYan Zhang More articles by this author , Jun YangJun Yang More articles by this author , Zhe TangZhe Tang More articles by this author , Tao WangTao Wang More articles by this author , Jihong LiuJihong Liu More articles by this author , and Shaogang WangShaogang Wang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1406AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Diabetes-induced erectile dysfunction (DED) is assumed to result from neurovascular abnormalitities. However, the entire picture of the molecular mechanisms underlying DED has not yet been clarified. To identify diabetes-related alterations in gene expression in erectile tissue that would provide novel diagnostic and therapeutic treatment targets to ameliorate DED. METHODS Molecular changes were assessed in erectile tissue of streptozotocin-induced Sprague-Dawley (SD) rats, in apomorphine (APO)-positive group and APO-negative group of diabetes. Differentially expressed genes were identified by microarrays and expression data validated by quantitative real-time PCR (qRT-PCR). We evaluated the effects of plasmid or adeno-associated virus (AAV) encoding the selected gene in cultured aortic endothelial cells (AECs) under high glucose and in vivo in the diabetic rats, respectively. Apomorphine test confirmed DED rats were intracavernosal administered AAV9-mediated S100A1(AAV-S100A1) or AAV9-green fluorescent protein (AAV-GFP) for four weeks. Age-matched rats were administered saline intracavernosally as normal control group. RESULTS The ICP/MAP ratio in the APO-positive group displayed a slight decrease compared with that in the normal control group, while APO-negative group exhibited moderate ED. We analyzed global gene expression in APO-positive group and APO-negative group, and focused on same changing trend within groups. In microarray analysis, 16 candidate genes were noted to be altered based on magnitude of expression changes, which includes 1 step up-regulated and 15 step down-regulated genes compared with the age matched normal controls. In vivo experiment exhibited erectile function in AAV-S100A1 group was markedly increased in the diabetic rats compared with the AAV-GFP groups. Mechanistically, S100A1 supplementation enhanced NO-cGMP and upstream VEGFR2/Akt signaling pathway. Consistented with in vivo experiments, in vitro study confirmed S100A1 compromised endothelial nitric oxide synthase (eNOS) activity in ECs by triggered the rapid cellular internalization of VEGFR2 and activated protein kinase C (PKC) hyperactivation which was blocked in the peresence of Calphostin-C. Moreover, transfection of AECs with small interfering RNA (siRNA) targeting either PKCα, δ, or ε confirmed that by regulating VEGFR2 expression and activation, PKC ε expression is critical for activation of Akt and eNOS by S100A1. CONCLUSIONS Microarray analysis identified 82 diabetic-related molecular alterations. Among them, S100A1 was significantly step-down regulated. S100A1 supplementation improves erectile function in rats with DED probably by its pro-angiogenic effects that associated with the increased expression, internalization of VEGFR2 and PKC ε hyperactivation. These finding provides evidence for a potential new target for DED management. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e581-e582 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Zhe Yu More articles by this author Yan Zhang More articles by this author Jun Yang More articles by this author Zhe Tang More articles by this author Tao Wang More articles by this author Jihong Liu More articles by this author Shaogang Wang More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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• W2796236462 title "MP43-07 INTRACAVERNOSAL ADENO-ASSOCIATED VIRUS MEDIATED S100A1 GENE TRANSFER ENHANCES ERECTILE FUNCTION IN DIABETIC RATS" @default.
• W2796236462 doi "https://doi.org/10.1016/j.juro.2018.02.1406" @default.
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