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 / 第二军医大学学报

ABSTRACT

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, 100 μg/ ml). The expression of LOX-1 and TGF-β1, mRNA was also determined by RT-PCR in the blank control group, ox-LDL (50 μg/ml) group and PIA(50 μg/ml ox-LDL+250 μg/ml PIA) group. The contents of TGF-β1 fibronectin (FN), and collagen IV (Col IV) 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 100 μg/ml ox - LDL groups was significantly higher than that of blank control group(P<0.05), with the highest expression found in the 50 μg/ml ox-LDL group; the expression of LOX-I and TGF-β 1 mRNA was significantly higher in 50 μg/ml ox-LDL group than that in the other 2 groups (P< 0.01). ELISA results demonstrated that the supernatant contents of TGF-β1, FN and Col IV were significantly higher in 50 μg/ml ox-LDL group than those in the other 2 groups (P< 0.05). Conclusion: Ox-LDL can upregulate the expression of LOX-1 and TGF-β1, 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.