You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I1 Apr 2017MP31-14 IMBALANCE BETWEEN MATRIX ETALLOPROTEINASE-1 (MMP-1) AND TISSUE INHIBITOR OF METALLOPROTEINASE-1 (TIMP-1) CONTRIBUTES TO INCREASED FIBROSIS OF BLADDER IN LONG-TERM DIABETIC RATS Rania Elrashidy, Zhenqun Xu, Firouz Daneshgari, and Guiming Liu Rania ElrashidyRania Elrashidy More articles by this author , Zhenqun XuZhenqun Xu More articles by this author , Firouz DaneshgariFirouz Daneshgari More articles by this author , and Guiming LiuGuiming Liu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.968AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Diabetes induces time-dependent structural and functional alterations in the urinary bladder. We have reported the actual collagen component did not change significantly in bladder of rats in the early stage of diabetes (>9 weeks after diabetes induction), but decreased as a percentage of the total tissue. This change may be related to the increased bladder compliance in rats with diabetes. However, no data is available in the long-term effects of diabetes on bladder structure. This study aimed to characterize bladder morphology in long-term diabetic rats, and to determine the potential mechanisms. METHODS Streptozotocin was used to induce diabetes in 8 weeks old male Sprague-Dawley rats, while age-matched control rats received vehicle (citrate buffer) only. Forty-four weeks after diabetes induction, bladders were harvested for morphological and molecular biological analysis. The bladder was sectioned at the equatorial midline. Masson′s Trichrome staining was performed. The stained slides were scanned, and the images were analyzed with Image-Pro Plus 5.1 image analysis software. The expression of collagen I, elastin, transforming growth factor beta-1 (TGF-β1), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in bladder was examined by immunoblotting. For comparison between control and diabetic group, two-tailed t-test was used. A P-value less than 0.05 was considered statistically significant. RESULTS Masson′s Trichrome staining and morphometrical analysis revealed increased deposition of collagen in lamina propria and among detrusor muscle fibers in diabetic rats, compared with controls. The results from the immunoblotting demonstrated significantly higher collagen I but lower elastin expression in diabetic bladders compared with that in controls. Diabetic rats displayed a marked increase in the protein expression of TGF-β1. This was associated with imbalance of the extracellular matrix turnover markers in diabetic bladders, evidenced by downregulation of MMP-1, along with upregulation of TIMP-1. CONCLUSIONS Our study demonstrated that long-term diabetes can induce increased fibrosis in bladder in rats, likely due to the upregulation of TGF-β1 and dysregulation of MMP-1/TIMP-1 system. These changes may contribute to the bladder dysfunction in the late stage of diabetes. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e404 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Rania Elrashidy More articles by this author Zhenqun Xu More articles by this author Firouz Daneshgari More articles by this author Guiming Liu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
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