Imbalance between matrix metalloproteinase‐1 (MMP‐1) and tissue inhibitor of metalloproteinase‐1 (TIMP‐1) contributes to bladder compliance changes in rabbits with partial bladder outlet obstruction (PBOO)

Abstract

What's known on the subject? and what does the study add?: A decrease in bladder compliance is known to be correlated with deterioration of renal function after bladder outlet obstruction (BOO). Increased deposition of extracellular matrix (ECM) in the detrusor layer is the primary reason for decreased compliance. In the bladder, as in other organs, ECM deposition is dependent on the balanced activity of proteolytic enzymes, including matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). The imbalance between MMPs and TIMPs is a key regulator in ECM turnover. It has been shown that an altered proteolytic balance between MMP-1 and TIMP-1 favours accumulation of ECM and decreases tissue compliance in an ovine fetal BOO model. Also, MMP-1 was significantly down-regulated, while TIMP-1 levels were increased, in a time- and pressure-dependent manner in a smooth muscle cell (SMC) mechanical strain model. In the present study we measured the bladder compliance of control, sham-operated and partial BOO (PBOO) rabbits using a UDS-600 urodynamic testing machine. Collagen deposition between and within the detrusor SM bundles was evaluated using Masson's Trichrome stain and transmission electron microscopy. The expression levels of MMP-1 and TIMP-1 were evaluated by Western blot. We found that the imbalance between MMP-1 and TIMP-1 favours accumulation of extracellular collagen, the structural components associated with decreased bladder compliance after PBOO. To investigate the underlying mechanisms of bladder compliance after partial bladder outlet obstruction (PBOO) and the role of the collagen degradation enzyme matrix metalloproteinase-1 (MMP-1) and its endogenous inhibitor tissue inhibitor of metalloproteinase-1 (TIMP-1) during this process. Bladder compliance of control, sham-operated and PBOO rabbits was measured using a UDS-600 urodynamic testing machine. Collagen deposition between and within the detrusor smooth muscle bundles was evaluated using Masson's Trichrome stain and transmission electron microscopy. The expression levels of MMP-1 and TIMP-1 were evaluated by Western blot. Bladder compliance decreased after PBOO. Collagen deposition increased both between and within the detrusor smooth muscle bundles, and had an inverse relationship with bladder compliance. MMP-1 and TIMP-1 expression negatively correlated with bladder compliance. These findings indicate that the imbalance between MMP-1 and TIMP-1 favours accumulation of extracellular collagen, the structural components associated with decreased bladder compliance after PBOO.