Effect of L158, 809 and Cilazapril on the Expression of TGF-β_1 and Secretion of Extracellular Matrix Proteins in Cultured Human Me-sangial Cells

摘要

Objective: To explore the effect of L158, 809 (angiatensin Ⅱ receptor Mockers, ARBs) and Cilazapril (Angiotensin converting enzyme inhibitor, ACEI) on the expression of transforming growth factor-β_1 (TGF-β_1) and secretion of fibronectin, laminin and type Ⅳ collagen from the cultured human mesangial cells . Methods: Human mesangial cells were cultured in different glucose (5.6 mmol/L and 30 mmol/L) and agents (1, 10, 100 and 500 μmol/L) concentrations . The proliferation of mesangial cells were detected at 24, 48 and 72 h . Then the mesangial cells are divided into four groups, low glucose (5.6 mmol/L) control group, high glucose (30 mmol/L) control group , L158, 809 (10 μmol/L) group and cilazapril (10 μmol/L) group. Forty- eight hours later, the expression of TGF-β_1 were detected by RT-PCR. Concentrations of TGF-β_1 , fibronection, laminin and type Ⅳ collagen in the su-pematants of the, mesangial cells were determined by EUSA and radioimmunoassay methods. Results: Compared with low glucose control group, the mesangial cells under high glucose medium show excessive proliferation and more TGF-β_1, fibronectin, laminin and type Ⅳ collagen in the supernatant. The expression of TGF-β_1 mRNA was also significantly increased under high glucose. The levels of TGF-β_1 and ECM (extracellular matrix) proteins in the L158, 809 group and cilazapril group are obviously lower than that of the high glucose control group. The expression of TGF-β_1 mRNA was markedly decreased in the L158, 809 group and cilazapril group compared with that of high glucose control group . Conclusion: High glucose stimulated the cultured human mesangial cells to excessively proliferate, express TGF-β_1 and secrete ECM proteins, and the high glucose-indeced changes were suppressed by either L158, 809 and cilazapril.