Effects of simvastatin and cilazapril on expressions of transforming growth factor-β_1 and insulin-like growth factor-I in cultured human glomerular mesangial cells

Objective To explore the effects of simvastatin and cilazapril on the expression of transforming growth factor-β_1 (TGF-β_1) and insulin-like growth factor-Ⅰ (IGF-Ⅰ) in the cultured human glomerular mesangial cells. Methods Human embryo glomerular mesangial cells were cultured in media with lower (5.6 mmol/L) or higher (30 mmol/L) glucose concentrations. Forty-eighthoursafteraddingsimvastatin(10 μmol/L)and/or cilazapril (10 μmol/L) to the cultured media, the concentrations of TGF-β_1, fibronection, laminin, type Ⅳ collagen proteins in the supernatant of cultured mesangial cells were determined by ELISA and radioimmunoassay and the expressions of TGF-β_1 and IGF-Ⅰ mRNA in cultured mesangial cells were also evaluated by RT-PCR. Results Compared with lower glucose control, the mesangial cells in the medium with higher glucose concentration showed excessive proliferation and higher expressions of TGF-β_1 and IGF-Ⅰ mRNA, and the levels of TGF-β_1, fibronection, laminin, and type Ⅳ collagen in the supernatant were also significantly increased. The expressions of TGF-β_1 and IGF-Ⅰ mRNA in the mesangial cells and the concentrations of TGF-β_1 and the extracellular matrix (ECM) proteins in the supernatant were all decreased after addition of simvastatin and cilazapril. Combination of simvastatin and cilazapril resulted in more profound suppressive effect on the expression of TGF-β_1 mRNA than either of them alone. Conclusion High concentration of glucose stimulates the cultured human mesangial cells excessively to express the TGF-β_1, IGF-Ⅰ and ECM proteins, and the high glucose-induced changes are suppressed by either simvastatin, cilazapril alone or combined treatment.