Expression of cytoskeletal proteins during the course of experimental diabetic nephropathy

Aims/hypothesis: Diabetic nephropathy is characterised by structural change s known to be associated in non-diabetic nephropathies with the expression of the cytoskeletal proteins alpha-smooth muscle actin and vimentin. We aim ed to investigate the expression of cytoskeletal proteins in experimental d iabetic nephropathy. Methods. Rats were made diabetic by an injection of streptozotocin (45 mg/k g). Groups of rats (n = 6) and their respective controls (n = 4) were kille d at different time intervals. (days 7, 15, 30, 60, 90 and 120). We also st udied two groups of diabetic rats treated with a long-acting insulin; the f irst (n = 8) was treated from the induction of diabetes and the second (n = 8) received insulin from day 15 onward. At each time-point, kidney functio n, proteinuria and histology were evaluated. Cytoskeletal proteins and coll agens III and IV deposition was determined by immunohistochemistry. Changes in the transcription of the cytoskeletal proteins was determined by northe rn blot analysis. Results. Although normal glomeruli did not express alpha-smooth muscle acti n until late in the time course, it was detected in diabetic mesangium from day 7 onward. In the interstitium, it appeared in a perivascular and perit ubular distribution. Vimentin was detectable within normal glomerular epith elial cells and increased rapidly (days 7 and 15) in diabetic rats. Vimenti n also appeared early within the lining of the peritubular capillaries and damaged diabetic tubules. These changes were associated with a delayed incr eased transcription of alpha-smooth muscle actin and vimentin. Treatment wi th insulin (early or late) attenuated and reversed respectively the express ion of cytoskeletal proteins and collagens within diabetic kidneys. Close c orrelations were noted between the number of alpha-smooth muscle actin posi tive cells within diabetic glomeruli and mesangial expansion (r = 0.46, p < 0.02) as well as interstitial alpha-smooth muscle actin positive cells and interstitial fibrosis (r = 0.51, p < 0.002). Conclusion/interpretation. Changes in the expression of cytoskeletal protei ns within the kidneys of diabetic rats suggest a role for alpha-smooth musc le actin and vimentin in the pathogenesis of diabetic kidney disease.