MOLECULAR MECHANISMS AND DYSREGULATED SUB-NETWORKS FOR BLADDER DYSFUNCTION IN TYPE 2 DIABETIC MICE

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research I1 Apr 2014MP1-18 MOLECULAR MECHANISMS AND DYSREGULATED SUB-NETWORKS FOR BLADDER DYSFUNCTION IN TYPE 2 DIABETIC MICE Sara Whitson, Guiming Liu, Mingfang Tao, Mark Chance, and Firouz Daneshgari Sara WhitsonSara Whitson More articles by this author , Guiming LiuGuiming Liu More articles by this author , Mingfang TaoMingfang Tao More articles by this author , Mark ChanceMark Chance More articles by this author , and Firouz DaneshgariFirouz Daneshgari More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.116AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Diabetes mellitus (DM) causes diabetic bladder dysfunction (DBD), which refers to a group of clinical symptoms that encompass storage problems such as overactive bladder and urge incontinence, voiding problems such as poor emptying or overflow incontinence, and other less clinically defined phenotypes such as decreased sensation and increased capacity. The pathophysiology of DBD includes the disturbances of the detrusor, urothelium, and autonomic nerves. However, the molecular changes of bladder in type 2 DM are not clear. In this study, we observed the molecular changes of detrusor muscle and urothelium separately in a type 2 DM mouse model. METHODS An in vitro labeling proteomics approach was applied to identify differentially expressed proteins between diabetic (TallyHo mice, n=4) and age-matched control (SWRJ mice, n=4) samples. Then, pathway analysis was conducted to investigate the molecular processes associated with DM using both the Ingenuity Pathway Analysis and Protein Analysis through Evolutionary Relationships; differentially expressed proteins were used to generate a protein-protein interaction network. To further explore and evaluate our findings, we selected upstream or downstream proteins for target validation by Western blot. RESULTS Tissue specificity was seen in the hydrophobic region of the chromatography and could serve as a tissue specific fingerprint. Running a four hour gradient, we were able to identify 1760 non-redundant proteins from the detrusor muscle and 3169 non-redundant proteins from the urothelium. Detrusor muscle samples had enrichment of cytoplasmic and plasma membrane proteins while urothelium samples showed elevated levels of nuclear proteins. Principle component analysis revealed a clear separation between the control and DM samples in each tissue which provided the basis for performing bioinformatic network analysis of the large dataset. The detrusor muscle samples showed DM induced increased tissue remodeling type events such as actin cytoskeleton signaling and signaling by Rho family GTPases. While the urothelium samples exhibited oxidative stress responses as seen in the suppression protein expression for key players in the mitochondrial dysfunction pathway, NRF-2 mediated oxidative stress response, and acute phase response canonical pathways. CONCLUSIONS These results suggested that diabetes induced an elevated inflammatory response, oxidative stress and tissue remodeling involved in the development of DBD in type 2 DM mice. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e8 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Sara Whitson More articles by this author Guiming Liu More articles by this author Mingfang Tao More articles by this author Mark Chance More articles by this author Firouz Daneshgari More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...