Effect of angiotensin II receptor blocker on TGF-β1, MMP-1, and collagen type I and type III concentration in New Zealand rabbit urethral stricture model
Authors Siregar S, Farenia R, Sugandi S, Roesli RM
Received 8 September 2017
Accepted for publication 26 April 2018
Published 2 October 2018 Volume 2018:10 Pages 127—133
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Jan Colli
Safendra Siregar, Reni Farenia, Suwandi Sugandi, Rully M Roesli
Urology Division, Department of Surgery, Hasan Sadikin Hospital Bandung, Faculty of Medicine Padjadjaran University, Bandung, Indonesia
Introduction: Urethral stricture is a disease with a high recurrence rate. Angiotensin II via AT1 receptor increases collagen formation through its effects on TGF-β1 and inhibition of collagenase activity. In this study, we evaluated the antifibrotic effect of angiotensin II receptor blocker on urethral stricture formation by creating a urethral stricture model in a male rabbit.
Material and methods: Thirty three male adult rabbits were separated into 3 groups (control, treatment, and sham). Group I consisted of 15 rabbits with urethral stricture that did not undergo any treatment, group II consisted of 15 rabbits with urethral stricture that were treated with a daily dose of 15 mg/kg losartan, given orally. Group III consisted of 3 rabbits with normal urethra and without any treatment. After 1, 2, and 4 weeks, the urethral tissues were collected, processed, and examined for TGF-β1, MMP-1, collagen type I, and collagen type III using enzyme-linked immunosorbent assay. Data were analyzed using 2-way analysis of variance using SPSS version 20.0.
Results: Urethral TGF-β1 concentration in the treatment group was significantly lower during the 2nd and 4th week of observation (p<0.0001), MMP-1 was significantly higher in the 1st, 2nd, and 4th week of observation (p<0.0001), collagen type I was significantly lower during the 2nd (p=0.001) and 4th week (p<0.0001), and collagen type III concentration was significantly lower in the 2nd and 4th week of observation (p<0.0001).
Conclusion: Angiotensin II receptor blocker could limit the progression of urethral stricture. The mechanism may be related to the AT1 blockage that leads to a decrease in TGF-β1 concentration, eventually resulting in lower collagen concentration due to increased MMP-1 activity.
Keywords: angiotensin receptor blocker, collagen, MMP-1, TGF-β1, urethral stricture
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