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

In diabetic nephropathy, a decrease in the activity of matrix metalloprotei nase (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 melli tus (DM) with streptozotocin. The level of glomerular gelatinolytic activit y 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). Gl omerular metalloproteinase migrated on gelatin zymography at positions repr esenting molecular weights of approximately 97, 80, 70 and 65 kDa. The inte nsity 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 thicken ing at 12 and 48 weeks respectively. These data suggest that the persistent decrease in glomerular gelatinolytic activity during the chronic phase con tributes to mesangial expansion and GBM thickening in DM rats. Moreover, th e activity may play different roles at the time of onset and during the pro gression of diabetic nephropathy.