Imbalance in extracellular matrix degradation in urethral stricture

BACKGROUND: Extracellular matrix degradation may play an important role in the etiology of urethral stricture. MMP1 and TIMP1 are involved in extracellular matrix degradation. The aim of this study was to investigate the roles of MMP1, TIMP1, and MMP1:TIMP1 ratio at the remodeling phase of urethral stricture in an animal model. METHODS: This research was carried out in collaboration between the Bogor Institute of Agriculture, Universitas Indonesia, and the Eijkman Institute Indonesia. This was an experimental in vivo study in adult male New Zealand rabbits, divided into two groups: a urethral stricture group and a control group. Euthanasia was performed in four rabbits of each group on days 7, 14, 21, 28, and 56. Urethral stricture was confirmed with an 8 F urethral catheter. Several laboratory examinations were done, including H&E and Masson trichrome staining, immunohistochemistry, and ELISA, to determine levels of MMP1 and TIMP1. Percentages of total collagen and collagen type 1 were counted with ImageJ 1.46q software. A general linear model was used for statistic analysis. RESULTS: We found that the level of MMP1 was lower, TIMP1 higher, and MMP1:TIMP1 ratio lower in the urethral stricture group than the control group. There was a correlation between MMP1 level with total collagen percentage (r=0.561, P=0.010) and no correlation between TIMP1 and total collagen (r=0.307, P=0.188). CONCLUSION: Imbalance in extracellular matrix degradation was marked by decreased MMP1 level and MMP1:TIMP1 ratio and increased TIMP1 level. This results showed that urethral stricture is not only caused by collagen decomposition, but also by the imbalance of extracellular matrix degradation.