Effect of L158,809 and Cilazapril on the Expression of TGF-β1 and Secretion of Extracellular Matrix Proteins in Cultured Human Mesangial Cells

Abstract：Objective: To explore the effect of L158,809 ( angiotensin Ⅱ receptor blockers, ARBs ) and Cilazapril ( Angiotensin converting enzyme inhibitor, ACEI ) on the expression of transforming growth factor-β1 ( TGF-β1 ) 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 500μmol/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 (10μmol/ L) group. Forty-eight hours later, the expression of TGF-β1 were detected by RT-PCR. Concentrations of TGF-β1 , fibronection, laminin and type Ⅳ collagen in the supernatants of the mesangial cells were determined by ELISA and radioimmunoassay methods.Results: Compared with low glucose control group, the mesangial cells under high glucose medium show excessive proliferation and more TGF-β1 , fibronectin, laminin and type Ⅳ collagen in the supernatant. The expressicn of TGF-β1 mRNA was also significantly increased under high glucose. The levels of TGF-β1 and ECM ( extracellular matrix ) proteins in the L 158,809 group and cilazapril group are obviously lower than that of the high glucose control group. The expression of TGF-β1 mRNA was markedly decreasedin 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 proliiferate, express TGF-β1 and secrete ECM proteins, and the high glucose-induced changes were suppressed by either L 158,809 and cilazapril.