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 mesangial expansion in diabetic nephropathy. To address this issue and the relationship between heparin's renoprotective and antimitogenic activities, we studied three streptozotocin-induced diabetic rat groups 5 and 12 months after diabetes induction: two groups were administered a modified heparin, each with a different protocol, and two healthy rat groups, one of which was treated with the same heparin, served as controls. Untreated diabetic animals developed clear evidence of nephropathy, namely expansion of the glomerular extracellular matrix, as expressed by glomerular basement membrane thickening, and increased mesangial deposition of type IV collagen. These alterations were prevented/cured by heparin treatment. Kidney sections were processed immunohistochemically for proliferating cell nuclear antigen and smooth muscle alpha-actin which is expressed only by proliferating mesangial cells. The number of proliferating cell nuclear antigen positive nuclei and alpha-actin-positive cells per glomerulus did not differ between groups at both 5 and 12 months. In conclusion, there is no evidence that mesangial proliferation is increased in late experimental diabetic nephropathy, and heparin seems to be renoprotective through mechanisms other than antiproliferation.