Effects of lovastatin on proliferation and extracellular matrix secretion in cultured rat mesangial cells

Purpose To investigate the effect of lovastatin on proliferation and extracellular matrix secretion of cultured rat mesangial cells. Methods Cultured rat mesangial cells were stimulated by platelet-derived growth factor(PDGF) in the absence or the presence of lovastatin and mevalonate metabolites. 5-Bromo-2-deoxyuridine incorporation was used to assess DNA synthesis. Collagen Ⅰ, Ⅳ and fibronectin were determined by enzyme-linked immunosorbent assay. Ras processing and mitogen-activated protein kinase activation were analyzed by Western blotting. Results Lovastatin caused a dose-dependent inhibition of DNA synthesis in cultured rat mesangial cells induced by PDGF, and Lovastatin suppressed Collagen Ⅰ, Ⅳ and fibronectin secretion. Lovastatin also inhibited PDGF-stimulated Ras processing and mitogen-activated protein kinase activation. Besides, mevalonic acid and geranylgeranyl pyrophosphate significantly prevented these inhibitory effect of lovastatin. Conclusion These results indicate that lovastatin may suppress mesangial proliferation and secretion of collagen Ⅳ, Ⅰ and fibronectin, which might be related to its inhibitory effect of mevalonate metabolites formation.