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MP31-14: 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

Saturday, May 13
9:30 AM - 11:30 AM
Location: BCEC: Room 156

Presentation Authors: Rania Elrashidy, Zagazig, Egypt, Zhenqun Xu, Shenyang, China, People's Republic of, Firouz Daneshgari, Guiming Liu*, Cleveland, OH

Introduction: 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&[prime]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&[prime]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.

Source Of Funding: NIH NIDDK 1R01 DK110567-01

Guiming Liu, PhD

Case Western Reserve University

Guiming Liu, PhD. Assistant Professor, Department of Surgery, MetroHealth Medical Center, Case Western reserve university, 2500 Metrohealth Dr, Cleveland, OH 44109
Dr. Liu's research focus is the lower urinary tract dysfunction, particularly, the bladder and urethral dysfunction in obesity and diabetes., including bladder overactivity, bladder underactivity, and urinary incontinence, etc.

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MP31-14: 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



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