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
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 re...
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Dove Medical Press
2018-10-01
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Series: | Research and Reports in Urology |
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Online Access: | https://www.dovepress.com/effect-of-angiotensin-ii-receptor-blocker-on-tgf-beta1-mmp-1-and-colla-peer-reviewed-article-RRU |
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author | Siregar S Farenia R Sugandi S Roesli RM |
author_facet | Siregar S Farenia R Sugandi S Roesli RM |
author_sort | Siregar S |
collection | DOAJ |
description | 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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language | English |
last_indexed | 2024-12-22T15:04:35Z |
publishDate | 2018-10-01 |
publisher | Dove Medical Press |
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series | Research and Reports in Urology |
spelling | doaj.art-28987613b6a64d938e5436334d240d452022-12-21T18:22:01ZengDove Medical PressResearch and Reports in Urology2253-24472018-10-01Volume 1012713341069Effect of angiotensin II receptor blocker on TGF-β1, MMP-1, and collagen type I and type III concentration in New Zealand rabbit urethral stricture modelSiregar SFarenia RSugandi SRoesli RMSafendra 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 stricturehttps://www.dovepress.com/effect-of-angiotensin-ii-receptor-blocker-on-tgf-beta1-mmp-1-and-colla-peer-reviewed-article-RRUAngiotensin Receptor BlockerCollagenMMP-1TGF-β1Urethral stricture |
spellingShingle | Siregar S Farenia R Sugandi S Roesli RM 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 Research and Reports in Urology Angiotensin Receptor Blocker Collagen MMP-1 TGF-β1 Urethral stricture |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | effect of angiotensin ii receptor blocker on tgf beta 1 mmp 1 and collagen type i and type iii concentration in new zealand rabbit urethral stricture model |
topic | Angiotensin Receptor Blocker Collagen MMP-1 TGF-β1 Urethral stricture |
url | https://www.dovepress.com/effect-of-angiotensin-ii-receptor-blocker-on-tgf-beta1-mmp-1-and-colla-peer-reviewed-article-RRU |
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