Effect of rosiglitazone on expression of pigment epithelium-derived factor and transforming growth factor-β1 in kidney of diabetic rats

Abstract

Objective To investigate the effect of rosiglitazone on the expression of pigment epithelium-derived factor (PEDF) and transforming growth factor-β1 (TGF-β1) in the kidney of diabetic rats. Methods A total of 42 healthy male SD rats (180 to 200 g) were randomly assigned to the normal control (NC) group (n=14), diabetes mellitus (DM) group (n=14), and rosiglitazone (RSG) treatment group (n=14). Diabetes was induced by an intraperitoneal injection of 55 μg/g streptozotocin. The rats in the RSG group were given rosiglitazone sodium 5 μg·g-1·d-1. At the end of 12 weeks, fasting blood glucose, kidney mass, kidney/body mass, 24-hour urinary albumin excretion (UAE), serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), high-density lipoprotein cholesterol (HDL-C), BUN, SCr and PEDF were measured. The expression of TGF-β1 and PEDF in the kidney was determined by immunohistochemical analysis and Western blot. Statistical analysis was performed using two-tail Student’s t test. Results Compared with the NC group, the DM group was characterized by the glomerular hypertrophy, mesangial expansion and glomerular basement membrane thickening; the protein expression of TGF-β1 was significantly increased (immunohistochemical analysis: 4.60±0.14 vs 1.57±0.14, t=3.052, P<0.01; Western blot: 1053±64 vs 462±70, t=2.817, P<0.01), whereas the protein expression of PEDF was significantly decreased (immunohistochemical analysis: 1.53±0.12 vs 3.96±0.18, t=2.845, P<0.01; Western blot: 228±275 vs 698±120, t=3.152, P<0.01) in the DM group. Compared with the DM group, the glomerular hypertrophy, mesangial expansion and glomerular basement membrane thickening were significantly ameliorated in the RGS group; the protein expression of TGF-β1 was significantly lower (immunohistochemical analysis: 2.79±0.16 vs 4.60±0.14, t=2.964, P<0.01; Western blot: 753±81 vs 1053±64, t=2.884, P<0.01), whereas the protein expression of PEDF was significantly higher (immunohistochemical analysis: 2.64±0.32 vs 1.53±0.12, t=2.347, P<0.05; Western blot: 473±127 vs 228±275, t=2.334, P<0.05) in the RSG treatment group. Conclusion Renoprotection of rosiglitazone on diabetic rats may be mediated by decreased expression of TGF-β1 and increased expression of PEDF. Key words: Diabetic nephropathy; Pigment epithelium-derived factor; Transforming growth factor-β1; Rosiglitazone