Effect of fluvastatin on expression of SGK1 and CTGF induced by aldosterone in rat mesangial cells

AIM: To investigate the effect of fluvastatin on the expression of serum and glucocorticoid inducible kinase 1 (SGK1) and connective tissue growth factor (CTGF) induced by aldosterone (Ald) in rat mesangial cells (GMCs). METHODS: GMCs were divided into (1) control group; (2) aldosterone group with different concentrations and times; (3) Ald (10-7 mol/L)+spironolactone (10-9mol/L) group; (4) Ald (10-7mol/L)+LY294002 (20 μmol/L) group; (5) Ald (10-7mol/L) +SB203580 (20 mmol/L) group; (6) the group of Ald (10-7mol/L)+ fluvastatin at different concentrations (10-7, 10-6, 10-5 mol/L); (7) Ald (10-7mol/L) +fluvastatin (10-5mol/L)+mevalonate (10-4 mol/L) group; (8) Ald (10-7mol/L) +fluvastatin (10-5mol/L)+FPP (farnesyl pyrophosphate, 10-4 mol/L) group; (9) Ald (10-7mol/L) +fluvastatin (10-5 mol/L) +GGPP (geranylgerany pyrophosphate, 10-4 mol/L) group. The protein levels of SGK1 and CTGF were determined by Western blotting. The levels of fibronection (FN), monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) in the supernatants were determined by enzyme-linked immunosorbant assay (ELISA). RESULTS: Aldosterone stimulated the protein expression of SGK1 and CTGF in cultured mesangial cells in a dose-dependent manner (P<0.01). SGK1 expression was increased at as early as 6 h (P<0.05), peaked at 12 h after aldosterone treatment (P<0.01). This stimulatory effect of aldosterone on SGK1 and CTGF was blocked by mineralocorticoid receptor (MR) inhibitor and LY294002 (a specific inhibitor of PI3K). Incubation of cells with fluvastatin significantly inhibited the aldosterone-induced the activations of SGK1 and CTGF, and the expression of MCP-1 and ICAM was in a dose-dependent manner (P<0.05). Exogenous mevalonate prevented the effect of fluvastatin on SGK1 expression in GMCs. CONCLUSION: Fluvastatin reduces aldosterone-induced SGK1 expression via mineralocorticoid receptor and PI3K pathway in rat mesangial cells. Such effect of flurastatin is partly blocked by mevalonate.