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-β₁ 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-β₁ 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-β₁ 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-β₁ and ECM proteins in GMCs under high concentration of glucose, partly by regulating the phosphorylation of p38 MAPK and CREB₁.