Rosiglitazone maleate inhibits the hyperexpression of RANTES induced by advanced glycosylation end products in human renal mesangial cells (HRMC)

Objective To investigate the effects of rosiglitazone on the upregulation of expression of chemokine RANTES (regulated upon activation,normal T cell expressed and secreted) induced by advanced glycosylation end products (AGEs) in the cultured human renal mesangial cells (HRMC). Methods AGE-BSA was prepared by incubation of bovine serum albumin (BSA) with glucose at 37℃ for 12 weeks.HRMC was cultured in the presence of AGE-BSA (glucose at 50 mmol/L) with rosiglitazone. RANTES mRNA was analyzed by quantitative real time RT-PCR.The contents of RANTES in the cultured supernatant and cell lysates were detected by using ELISA and Western blot,respectively. Diabetic rats induced by streptozotocin were treated with or without rosiglitazone.The AGE-Peptide level in serum was measured by flow injection assay.Immunohistochemistry was applied to detect the expression of RANTES in renal cortex of rats.Results Group of AGE treated with rosiglitazone (RSG) at 0.1,1,10,100μmol/L versus AGE without RSG showed the inhibited effects on RANTES mRNA (0.22,0.20,0.14,0.12 vs 0.45,P0.05～0.01).Serum level of AGE-Peptiede was higher in DM versus control(2,87±0.21 vs 0.90±0.13U/ml,P0.01),and lower in DM+RSG than DM (1.45±0.15 vs 2.87±0.21U/ml,P0.01).The RANTES(+) particles number each glomerulus was more in DM versus control(8.97±0.9 vs 0.93±0.6,P0.05) ,and less in DM+RSG than DM(5.01±0.6 vs 8.97±0.9,P 0.05).Conclusions Rosiglitazone significantly inhibits the expression and secretion of RANTES induced by AGE-BSA in vivo and in vitro.