THE EFFECT OF LOVASTATIN ON THE EXPRESSION OF TRANSFORMING GROWTH FACTOR、β_1 AND EXTRACELLULAR MATRIX IN THE HUMAN MESANGIAL CELLS

Objective: To observe the effect of statin on the expression of transforming growth factor、β_1 (TGF、β_1) and the secretion of fibronectin, laminin and type IV collagen proteins from the cultured human mesangial cells. Methods: The expression of TGF、β_1 mRNA in mesangial cells exposed to low glucose (5.6 mol/L) and high glucose (30 mol/L) level were determined by RT、PCR method. The concentrations of TGF、β_1, fibronectin, laminin and type IV collagen before and after the addition of lovastatin, cilazapril or both were assessed by ELISA and radioimmunoassay methods respectively. The TGF、β_1 mRNA expressions of mesangial cells were also detected after 48 hour stimulation of lovastatin and cilazapril. Results: Glucose in high concentration induced over proliferation of mesangial cells, increased the expression of TGF、β_1 mRNA and the concentrations of TGF、β_1, fibronection, laminin and type IV collagen in the supernatant. Both lovastatin and cilazapril decreased the cell proliferation, the TGF、β_1 mRNA expression and the concentrations of TGF、β_1 and such extrocellular matrix (ECM) proteins. The combination of lovastatin and cilazapril was more potent than lovastatin or cilazapril alone. Conclusions: Glucose in high concentration stimu、lates the cultured human mesangial cells to express the TGF、β_1 and extrocellular matrix proteins excessively, and the high glucose、induced changes can be suppressed by either lovastatin or cilazapril alone or in combination. These results suggest that statin has a direct cellular impact on the expression of TGF、β_1 and ECM proteins, which is independent of the cholesterol、lowering effect.