Mesangial cell proliferation in long-term streptozotocin-induced diabetes mellitus in the rat and the renoprotective activity of heparin

At present, it is not clear whether mesangial proliferation underlies mesan gial expansion in diabetic nephropathy. To address this issue and the relat ionship between heparin's renoprotective and antimitogenic activities, we s tudied three streptozotocin-induced diabetic rat groups 5 and 12 months aft er diabetes induction: two groups were administered a modified heparin, eac h with a different protocol, and two healthy rat groups, one of which was t reated with the same heparin, served as controls. Untreated diabetic animal s developed clear evidence of nephropathy, namely expansion of the glomerul ar extracellular matrix, as expressed by glomerular basement membrane thick ening, and increased mesangial deposition of type IV collagen. These altera tions were prevented/cured by heparin treatment. Kidney sections were proce ssed immunohistochemically for proliferating cell nuclear antigen and smoot h muscle a-actin which is expressed only by proliferating mesangial cells. The number of proliferating cell nuclear antigen positive nuclei and a-acti n-positive cells per glomerulus did not differ between groups at both 5 and 12 months. In conclusion, there is no evidence that mesangial proliferatio n is increased in late experimental diabetic nephropathy, and heparin seems to be renoprotective through mechanisms other than antiproliferation.