caa a22 4500 475770951 CHVBK 20180406123616.0 cr unu---uuuuu 170329e20000101xx s 000 0 eng 10.1007/s001250050012 doi (NATIONALLICENCE)springer-10.1007/s001250050012 Expression of cytoskeletal proteins during the course of experimental diabetic nephropathy [Elektronische Daten] [T. Sanai, T. Sobka, T. Johnson, M. El-Essawy, E. C. Muchaneta-Kubara, O. Ben Gharbia, S. Oldroyd, A. M. El Nahas] Aims/hypothesis: Diabetic nephropathy is characterised by structural changes known to be associated in non-diabetic nephropathies with the expression of the cytoskeletal proteins a-smooth muscle actin and vimentin. We aimed to investigate the expression of cytoskeletal proteins in experimental diabetic nephropathy.¶Methods. Rats were made diabetic by an injection of streptozotocin (45 mg/kg). Groups of rats (n = 6) and their respective controls (n = 4) were killed at different time intervals. (days 7, 15, 30, 60, 90 and 120). We also studied two groups of diabetic rats treated with a long-acting insulin; the first (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 function, proteinuria and histology were evaluated. Cytoskeletal proteins and collagens III and IV deposition was determined by immunohistochemistry. Changes in the transcription of the cytoskeletal proteins was determined by northern blot analysis.¶Results. Although normal glomeruli did not express α-smooth muscle actin 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 peritubular distribution. Vimentin was detectable within normal glomerular epithelial cells and increased rapidly (days 7 and 15) in diabetic rats. Vimentin also appeared early within the lining of the peritubular capillaries and damaged diabetic tubules. These changes were associated with a delayed increased transcription of α-smooth muscle actin and vimentin. Treatment with insulin (early or late) attenuated and reversed respectively the expression of cytoskeletal proteins and collagens within diabetic kidneys. Close correlations were noted between the number of α-smooth muscle actin positive cells within diabetic glomeruli and mesangial expansion (r = 0.46, p < 0.02) as well as interstitial α-smooth muscle actin positive cells and interstitial fibrosis (r = 0.51, p < 0.002).¶Conclusion/interpretation. Changes in the expression of cytoskeletal proteins within the kidneys of diabetic rats suggest a role for α-smooth muscle actin and vimentin in the pathogenesis of diabetic kidney disease. [Diabetologia (2000) 43: 91-100] Springer-Verlag Berlin Heidelberg, 2000 Keywords Diabetic nephropathy, cytoskeletal proteins, α-smooth muscle actin, vimentin nationallicence Sanai T. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut Sobka T. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut Johnson T. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut El-Essawy M. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut Muchaneta-Kubara E. C. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut Ben Gharbia O. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut Oldroyd S. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut El Nahas A. M. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut https://doi.org/10.1007/s001250050012 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250050012 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sanai T. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut NATIONALLICENCE 700 1- Sobka T. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut NATIONALLICENCE 700 1- Johnson T. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut NATIONALLICENCE 700 1- El-Essawy M. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut NATIONALLICENCE 700 1- Muchaneta-Kubara E. C. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut NATIONALLICENCE 700 1- Ben Gharbia O. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut NATIONALLICENCE 700 1- Oldroyd S. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut NATIONALLICENCE 700 1- El Nahas A. M. Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, UK, GB aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer