Expression of serum and glucocorticoid-inducible kinase1 in diabetic rats and its modulation by fluvastatin.
The expression of serum and glucocorticoid-induced protein kinase in the renal cortex of diabetic rats was examined, and the function of signal transduction mediated by SGK1 in diabetic nephropathy and its modulatiqn by fluvastatin were also investigated. 24 male Wistar rats were randomly divided into normal control group (n = 8), diabetic nephropathy group (n = 8) and fluvastatin-treated diabetic nephropathy group (15 mg/kg/d, n = 8). The metabolic parameters were measured at the 8th week. The expression of transforming growth factor beta1 (TGF-beta1) and fibronectin (FN) was immunohistochemically examined. The expression of SGK1 was detected by RT-PCR and Western blot, and CTGF mRNA was assessed by RT-PCR. As compared to DN, blood glucose, 24-h urinary protein, Cer and kidney weight index were all decreased and the weight was increased obviously in group F. At the same time, mesangial cells and extracellular matrix proliferation were relieved significantly. The levels of cortex SGK1 mRNA and protein were up-regulated, and both TGF-beta1 and FN were down-regulated by fluvastatin. The mRNA of SGK1 was positively correlated with the CTGF, TGF-beta1 and FN. SGK1 expression is markedly up-regulated in the renal cortex of DN group and plays an important role in the development and progress of diabetic nephropathy by means of signal transduction. Fluvastatin suppressed the increased SGK1mRNA expression in renal cortex and postponed the development of diabetic nephropathy.
Wang
Xuebin
X
Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Luo
Changqing
C
Liu
Jianshe
J
Zhang
Chun
C
Wang
Yumei
Y
Zhu
Zhonghua
Z
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D007211:Indoles / Q000494:pharmacology*; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D000099184:Serum-Glucocorticoid Regulated Kinases
D005229:Fatty Acids, Monounsaturated; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017874:Immediate-Early Proteins; D007211:Indoles; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D000099184:Serum-Glucocorticoid Regulated Kinases