153 Effect of Simvastatin on Transforming Growth Factor BETA-1-Induced Myofibroblast Differentiation and Collagen Production in Nasal Polyp-Derived Fibroblasts

BACKGROUND: Statins are the most commonly prescribed drugs for the treatment of hypercholesterolemia. Statins exert not only lipid-lowering but also other cellular effects, including anti-fibrotic properties. The purposes of this study were to determine the effect of simvastatin on Transforming growth factor (TGF)-β1-induced myofibroblast differentiation and collagen production in nasal polyp-derived fibroblasts (NPDFs) and to verify the mechanism of the effect of simvastatin in TGF-β1-induced myofibroblast differentiation in NPDFs. METHODS: NPDFs were pre-treated with simvastatin with or without mevalonate or Y-27643 for 2 hours prior to induction by TGF-β1. The expression of α-smooth muscle actin (SMA) and collagen type IV mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of α-SMA protein was determined by immunofluoescent cytochemical staining. Total soluble collagen production was analyzed by the SirCol collagen dye-binding assay. Phosphorylation of Smad 2/3 was evaluated by Western blot analysis. RESULTS: In TGF-β1-induced NPDFs, simvastatin significantly inhibited the expressions of α-SMA and collagen type IV mRNA and reduced α-SMA and collagen protein levels. Pre-treatment with mevalonate reversed the effect of simvastatin. The expression of α-SMA mRNA and protein was significantly decreased by pre-treatment with Y-27632. The TGF-β1-induced expression of pSmad 2/3 protein was notably decreased by pre-treatment with simvastatin. CONCLUSIONS: We showed that simvastatin inhibits TGF-β1-induced myofibroblast differentiation (expression of α-SMA) and collagen production in NPDFs and Rho/Rock and TGF-β/Smad signaling is involved as an underlying mechanism. The results of our study suggest that simvastatin is a possible candidate for the suppression of nasal polyp formation.