Long-term change of glomerular gelatinolytic activity in rats with streptozotocin-induced diabetes

In diabetic nephropathy, a decrease in the activity of matrix metalloproteinase (MMP) might contribute to the build-up of extracellular matrix protein in the mesangium and the glomerular basement membrane (GBM). Levels of MMP activity were measured as gelatinolytic activity in glomerular homogenates isolated from rats 1, 4, 12, 24 and 48 weeks after inducing diabetes mellitus (DM) with streptozotocin. The level of glomerular gelatinolytic activity after 1 week in DM rats was significantly increased compared with that in controls (224.8% of control; DM vs. control, 13.58 vs. 6.04 mU/glomerulus; P < 0.05), then decreased by 48 weeks (week 4, 92.8% of control; week 12, 81.9% of control; week 24, 31.8% of control; week 48, 47.3% of control). Glomerular metalloproteinase migrated on gelatin zymography at positions representing molecular weights of approximately 97, 80, 70 and 65 kDa. The intensity of these lytic bands was increased at 1 week but decreased at 24 and 48 weeks. Light microscopy revealed hypercellularity in the mesangial area at 1 week, followed by mild and marked mesangial expansion with GBM thickening at 12 and 48 weeks respectively. These data suggest that the persistent decrease in glomerular gelatinolytic activity during the chronic phase contributes to mesangial expansion and GBM thickening in DM rats. Moreover, the activity may play different roles at the time of onset and during the progression of diabetic nephropathy.