[Effects of fluvastatin on the activation of p38 mitogen-activated protein kinase in glomerular mesangial cells under high concentration of glucose].
This study is to investigate the effects of fluvastatin on the activation of p38 mitogen-activated protein kinase (p38 MAPK) and cAMP response element-binding protein (CREB1) in glomerular mesangial cells under high concentration of glucose. High concentration glucose and fluvastatin were used to stimulate the cultured rat glomerular mesangial cells (GMCs) in vitro. The protein expressions of p38 MAPK, CREB1, p-p38 MAPK and p-CREB1 were observed with Western blotting. TGF-beta1 and fibronectin (FN) mRNA were measured with reverse transcription and polymerase chain reaction (RT-PCR). The protein synthesis of laminine (LN) and type IV collagen in the supernatants of the GMCs were detected with radioimmunoassay. Compared with low glucose control group, the expressions of p-p38 MAPK, p-CREB1 were increased obviously in high glucose group, TGF-beta1 mRNA and FN mRNA, LN and type IV collagen in the supernatants were increased significantly in GMCs under high concentration glucose medium. The expression levels of p-p38 MAPK, p-CREB1, TGF-beta1 mRNA, and FN mRNA, LN and type IV collagen in the supernatants were significantly lower in the fluvastatin group than those in the high concentration glucose group. It is concluded that fluvastatin can inhibit over production of TGF-beta1 and ECM proteins in GMCs under high concentration of glucose, partly by regulating the phosphorylation of p38 MAPK and CREB1.
Wang
Li-Hui
LH
Department of Nephrology, Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China. wanglh68@163.com
Wu
Guang-Li
GL
Zhang
Li-Xia
LX
Huang
Xu-Dong
XD
Li
Sai
S
D000599:Amino Acids, Diamino / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D000077340:Fluvastatin; D005947:Glucose / Q000008:administration & dosage; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000599:Amino Acids, Diamino; D024141:Collagen Type IV; D017362:Cyclic AMP Response Element-Binding Protein; D005229:Fatty Acids, Monounsaturated; D005353:Fibronectins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C045397:laminine; D000077340:Fluvastatin; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose