saRNA Guided iNOS Up-Regulation Improves Erectile Function of Diabetic Rats

No AccessJournal of UrologyInvestigative Urology1 Aug 2013saRNA Guided iNOS Up-Regulation Improves Erectile Function of Diabetic Rats Tao Wang, Mingchao Li, Huixin Yuan, Yin Zhan, Hua Xu, Shaogang Wang, Weiming Yang, Jihong Liu, Zhangqun Ye, and Long-Cheng Li Tao WangTao Wang More articles by this author , Mingchao LiMingchao Li More articles by this author , Huixin YuanHuixin Yuan More articles by this author , Yin ZhanYin Zhan More articles by this author , Hua XuHua Xu More articles by this author , Shaogang WangShaogang Wang More articles by this author , Weiming YangWeiming Yang More articles by this author , Jihong LiuJihong Liu More articles by this author , Zhangqun YeZhangqun Ye More articles by this author , and Long-Cheng LiLong-Cheng Li More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.03.043AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Promoter targeted saRNAs mediate sequence specific up-regulation of gene expression. We explored the therapeutic effect of RNA activation mediated iNOS gene activation on improving erectile function in a rat model of diabetes mellitus. Materials and Methods: An optimal saRNA sequence specific for iNOS promoter was cloned into an adenoviral vector, resulting in AdU6/shiNOS and AdU6/shControl. The corresponding viruses were used to transduce cultured rat cavernous smooth muscle cells. Streptozotocin induced diabetes models were established in rats and used to test the effects of intracavernous delivery of iNOS saRNA viruses on erectile function. iNOS expression in the cavernous smooth muscle cells or penile tissue of treated rats was assessed by reverse transcriptase-polymerase chain reaction and Western blot. Cyclic guanosine monophosphate was analyzed by enzyme-linked immunosorbent assay. Intracavernous pressure in response to cavernous nerve stimulation was measured using a data acquisition system on post-injection days 1, 3, 5, 7, 10 and 14. Results: Adenovirus mediated expression of iNOS saRNA caused sustained up-regulation of iNOS in cavernous smooth muscle cells. Intracavernous injection of AdU6/shiNOS activated iNOS expression in vivo and significantly increased peak intracavernous pressure in streptozotocin induced diabetic rats via nitric oxide/intracellular cyclic guanosine monophosphate activation. Conclusions: Results show that saRNA mediated iNOS over expression in the penis can restore erectile function in streptozocin diabetic rats via the nitric oxide-cyclic guanosine monophosphate pathway. References 1 : Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol1994; 151: 54. Abstract, Google Scholar 2 : Do impotent men with diabetes have more severe erectile dysfunction and worse quality of life than the general population of impotent patients?: Results from the Exploratory Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database. 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Google Scholar Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China, and Department of Urology and Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco (LCL), San Francisco, California© 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited bySeftel A (2018) Re: Prevalence of Erectile Dysfunction and Associated Factors among Diabetic Men Attending Diabetic Clinic at Muhimbili National Hospital in Dar-es-Salaam, TanzaniaJournal of Urology, VOL. 193, NO. 4, (1325-1326), Online publication date: 1-Apr-2015.Silva C, Nunes K, Torres F, Cassoli J, Santos D, Almeida F, Matavel A, Cruz J, Santos-Miranda A, Nunes A, Castro C, Machado de Ávila R, Chávez-Olórtegui C, Láuar S, Felicori L, Resende J, Camargos E, Borges M, Cordeiro M, Peigneur S, Tytgat J and de Lima M (2018) PnPP-19, a Synthetic and Nontoxic Peptide Designed from a Phoneutria nigriventer Toxin, Potentiates Erectile Function via NO/cGMPJournal of Urology, VOL. 194, NO. 5, (1481-1490), Online publication date: 1-Nov-2015. Volume 190Issue 2August 2013Page: 790-798 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.KeywordsRNAdiabetes mellitus, experimentalpenisnitric oxide synthase type IIerectile dysfunctionMetricsAuthor Information Tao Wang More articles by this author Mingchao Li More articles by this author Huixin Yuan More articles by this author Yin Zhan More articles by this author Hua Xu More articles by this author Shaogang Wang More articles by this author Weiming Yang More articles by this author Jihong Liu More articles by this author Zhangqun Ye More articles by this author Long-Cheng Li More articles by this author Expand All Advertisement PDF downloadLoading ...