Oxidized low density lipoprotein-induced expression of transforming growth factor beta 1 and production of extracellular matrix in rat glomerular mesangial cells is mediated by lectin-like oxidized low density lipoprotein receptor-1

Objective:To investigate the effect of oxidized low-density lipoprotein(ox-LDL)on expression of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1),transforming growth factor beta 1(TGF-β_1),and secretion of extracelluar matrix(ECM)in cultured rat glomerular mesangial cells(GMCs),and to investigate the influence of LOX-1 inhibitor polyinosinic acid(PIA)on the effect of ox-LDL.Methods:Rat glomerular masengial cells were cultured in vitro.RT-PCR was employed to determine the LOX-1 mRNA expression in GMCs incubated with different concentrations of ox-LDL(0,25,50, 100μg/ml).The expression of LOX-1 and TGF-β_1 mRNA was also determined by RT-PCR in the blank control group,ox-LDL (50μg/ml)group and PIA(50μg/ml ox-LDL+250μg/ml PIA)group.The contents of TGF-β_1,fibronectin(FN),and collagenⅣ(ColⅣ)in the supernatants of the above 3 groups were determined by ELISA.Results:RT-PCR showed that LOX-1 mRNA expression in 25,50 and 100μg/ml ox-LDL groups was significantly higher than that of blank control group(P0.05),with the highest expression found in the 50μ/ml ox-LDL group;the expression of LOX-1 and TGF-β_1 mRNA was significantly higher in 50μg/ml ox-LDL group than that in the other 2 groups(P0.01).ELISA results demonstrated that the supernatant contents of TGF-β_1,FN and ColⅣwere significantly higher in 50μg/ml ox-LDL group than those in the other 2 groups(P0.05).Conclusion:Ox-LDL can upregulate the expression of LOX-1 and TGF-β_1 mRNA and the secretion of extracelluar matrix in GMCs.Polyinosinic acid can antagonize the above effect of ox-LDL,suggesting that LOX-1 may participate in ox-LDL- induced GMCs damage and is involved in the development and progression of glomerulosclerosis.