Diabetic vascular complication is one of the leading causes of end stage renal disease (ESRD). ESRD in diabetic patients significantly increases the risk of cardiovascular complications. Pathobiologic changes in diabetes results in increased production of advanced glycosylation end product with upregulation of cytokines and growth factors. In this study we aim to elucidate the role of various vascular growth factors and cytokines in the development of diabetic nephropathy.

Methods: 

Diabetes was induced in Watanabe heritable hyperlipidemic (WHHL) rabbits (n=30) using intravenous injection of alloxan and another set of WHHL rabbits served as control (n=30). The animals were sacrificed 4 weeks, 12 weeks and 24 weeks after induction of diabetes and renal tissue was harvested. The expression patterns of vascular growth factors in the renal tissues were analyzed using immunohistochemistry and real time RT-PCR.

Results: 

We observed a significant increase in Vascular Growth Factor-A (VEGF-A) expressions in podocytes and parietal epithelium of glomeruli at 8 and 12 week time point. However, the VEGF-A expressions were significantly reduced at 24 weeks. Transforming growth factor-b (TGF-b) expression was increased in diabetic animals at all time points. We observed increased macrophage infiltration and Nuclear factor kappa-B (NF kB) expressions in periglomerular region of renal cortex at 4 and 8 week time point.

Conclusions: 

We conclude that in alloxan induced experimental diabetes, variable expressions of VEGF-A occur in renal tissue depending on the duration of the diabetes. The VEGF-A expressions are presumably modulated by inflammatory processes in diabetic renal disease.