The Effect Of Valsartan On The Expression Of The Receptor For Advanced Glycation End Products In Human Glomerular Mesangial Cells

【OBJECTIVE】To observe the effect of valsartan on human glomerular mesangial cells oxidative stress and the expression of the receptor for advanced glycation end-products (RAGE) induced by the advanced glycation end-products (AGEs), expecting to elucidate the impact of the antioxidant properties of valsartan on RAGE expression.【METHODS】1. Human glomerular mesangial cells were treated with advanced glycation end-product-bovine serum albumin (AGE-BSA) , or nonglycated BSA, or tertiary butyl hydrogen peroxide (t-BHP) for 24h, 48h, and observed the peroxide, which is the key member of the reactive oxygen species (ROS), to reflect oxidative stress level, and RAGE expression in mesangial cells. The peroxide in cells was measured by Flow cytometry, using DCFH-DA label. The mRNA of RAGE was detected by semi-quantitative reberse transcription polymerase chain reaction (RT-PCR) and the RAGE protein was assayed by immunocytochemistry. 2. Mesangial cells were treated with 200mg/L AGE-BSA in the presence of valsartan of different concentrations for 12h, 24h, 48h, and then detected the expression of RAGE, ROS , and the mRNA of p22phox, p47 phox , which were the primary subunits of NADPH oxidase, in order to investigate the valsartan's effect on the the expression of RAGE, oxidative stress and NADPH oxidase evoked by AGE-BSA.【RESULTS】1. The expression of RAGE and peroxide in mesangial cells ,which were treated with 200mg/L AGE-BSA or t-BHP for 24h, 48h, were up-regulated compared with the control groups with exposure time increasing , while the peroxide and the expression of RAGE in the groups intervened by N- Acetylcysteine were down-regulated. 2. Valsartan dose-dependently inhibited the AGE-elicited overexpression of RAGE, peroxide and p47phox in mesangial cells, but it did not influence p22phox mRNA level for 12h, 24h, 48h.【CONCLUSIONS】1. Treatment of mesangial cells with AGE-BSA could induce intracellular oxidative stress, thereby leading to the expression of RAGR mRNA and protein. 2. Valsartan could inhibit the up-regulated of RAGE products and oxidative stress induced by AGE-BSA in a dose-dependent manner. Valsartan could down-regulate AGEs-induced RAGE expression through its antioxidant properties.