Effects of valsartan on expression of p38MAPK signal transduction pathway in glomerular mesangial cells under high concentration of glucose

Aim To investigate the effects of valsartan on the expression of TGF-β1 mRNA and the activation of p38 mitogen-activated protein kinase(p38MAPK),mitogen activated protein kinase kinasse3/6(MKK3/6)and cAMP response element-binding protein1(CREB1) in glomerular mesangial cells under high concentration of glucose.Methods High concentration glucose and valsartan were used to stimulate the cultured rat GMCs in vitro.The protein expressions of p38 MAPK,CREB1,p-p38 MAPK,p-MKK3/6 and p-CREB1 were observed by Western blot analysis.TGF-β1 and fibronectin(FN) mRNA were measured by reverse transcription and polymerase chain reaction(RT-PCR).The protein synthesis of FN and type Ⅳ collagen in the supernatants of the GMCs was detected by radioimmunoassay.Results Compared with low glucose control group,the expressions of p-p38 MAPK,p-MKK3/6,p-CREB1 protein,TGF-β1 and FN mRNA,FN and type Ⅳ collagen in the supernatants were significantly increased in GMCs under high concentration glucose medium.The expression levels of p-p38 MAPK,p-MKK3/6 and p-CREB1 were significantly lower in the valsartan group than those in the high concentration glucose group.So did the mRNA of TGF-β1 and FN.The concentration of FN and type Ⅳ collagen in the supernatants in the valsartan group was lower than that in the high concentration glucose control group.Conclusion Valsartan 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,MKK3/6 and CREB1.