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. Objective• 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. Materials and Methods• 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. Results• 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. Conclusion• 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.

Inhibition of HIF Reduces Bladder Hypertrophy and Improves Bladder Function in Murine Model of Partial Bladder Outlet Obstruction

“…All of these genes have been reported to have key roles in PBOO induced bladder pathogenesis. 5,7,8,10,20 Treatment with 17-DMAG decreased PBOO induced up-regulation of the Tgfb, Glut1, Flt-1 and Timp-1 genes whereas the expression level of Vegf was similar to that in the placebo group (2.8-fold vs 2.2-fold increase vs the Sham plus P group). Many stimuli, including growth factors, hormones and cytokines, regulate Vegf expression at the transcriptional level.…”

M3 receptor modulates extracellular matrix synthesis via ERK1/2 signaling pathway in human bladder smooth muscle cells

“…In the bladder, as in other organs, the ratio of MMPs and TIMPs is critical in the regulation of ECM turnover. During BOO, the imbalance between MMP1 and TIMP‐1 was found to be associated with the accumulation of extracellular collagen and decreased bladder compliance 20 . However, to date, there is no further study stepping in the causes of this imbalance.…”

Alveolarization Genes Modulated by Fetal Tracheal Occlusion in the Rabbit Model for Congenital Diaphragmatic Hernia: A Randomized Study

“…Negative controls were realized by omission of the primary antibody. Primary antibodies have been confirmed to cross-react with rabbit tissue [42–44]. Subsequently the sections were washed with TBS and treated for 30 minutes at room temperature either with undiluted EnVision+ HRP complex (Dako), or with mouse anti-goat biotinylated secondary antibody (sc-53799, Santa Cruz; 1:200), followed by Vectastain ABC kit reagents according to the manufacturer’s instructions (Vector Laboratories, Burlingame, CA).…”