Effect of simvastatin on transforming growth factor beta-1-induced myofibroblast differentiation and collagen production in nasal polyp-derived fibroblasts

Il Ho Park, Se Jin Park, Jung Sun Cho, You Mi Moon, Jun Hyeok Moon, Tae-Hoon Kim, Sang Hag Lee, Heung Man Lee

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 antifibrotic properties. The purpose of this study was to determine the effect of simvastatin on transforming growth factor (TGF)-beta-1-induced myofibroblast differentiation and collagen production in nasal polyp- derived fibroblasts (NPDFs) and to verify the mechanism of the effect of simvastatin in TGF-beta-1-induced myofibroblast differentiation in NPDFs. Methods: NPDFs were pretreated with simvastatin with or without mevalonate or Y-27643 for 2 hours before induction by TGF-beta-1. The expression of alpha-smooth muscle actin (SMA) and collagen type IV mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of alpha-SMA protein was determined by immunofluorescent cytochemical staining. Total soluble collagen production was analyzed by the SirCol collagen dye-binding assay (Biocolor, Belfast, U.K.). Phosphorylation of Smad 2/3 was evaluated by Western blot analysis. Results: In TGF-beta-1-induced NPDFs, simvastatin significantly inhibited the expressions of α-SMA and collagen type IV mRNA and reduced alpha-SMA and collagen protein levels. Pretreatment with mevalonate reversed the effect of simvastatin. The expression of alpha-SMA mRNA and protein was significantly decreased by pretreatment with Y-27632. The TGF-beta-1-induced expression of pSmad 2/3 protein was notably decreased by pretreatment with simvastatin. Conclusion: We showed that simvastatin inhibits TGF-beta-1-induced myofibroblast differentiation (expression of alpha-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.

Original languageEnglish
Pages (from-to)7-11
Number of pages5
JournalAmerican Journal of Rhinology and Allergy
Volume26
Issue number1
DOIs
Publication statusPublished - 2012 Jan 1

Fingerprint

Nasal Polyps
Simvastatin
Myofibroblasts
Transforming Growth Factor beta
Collagen
Fibroblasts
Smooth Muscle
Actins
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Mevalonic Acid
Collagen Type IV
Messenger RNA
Proteins
Muscle Proteins
Transforming Growth Factors
Hypercholesterolemia
Reverse Transcription
Coloring Agents
Western Blotting
Phosphorylation

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Immunology and Allergy

Cite this

@article{afdc6846b80445e58fafd65cf9d08f24,
title = "Effect of simvastatin on transforming growth factor beta-1-induced myofibroblast differentiation and collagen production in nasal polyp-derived fibroblasts",
abstract = "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 antifibrotic properties. The purpose of this study was to determine the effect of simvastatin on transforming growth factor (TGF)-beta-1-induced myofibroblast differentiation and collagen production in nasal polyp- derived fibroblasts (NPDFs) and to verify the mechanism of the effect of simvastatin in TGF-beta-1-induced myofibroblast differentiation in NPDFs. Methods: NPDFs were pretreated with simvastatin with or without mevalonate or Y-27643 for 2 hours before induction by TGF-beta-1. The expression of alpha-smooth muscle actin (SMA) and collagen type IV mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of alpha-SMA protein was determined by immunofluorescent cytochemical staining. Total soluble collagen production was analyzed by the SirCol collagen dye-binding assay (Biocolor, Belfast, U.K.). Phosphorylation of Smad 2/3 was evaluated by Western blot analysis. Results: In TGF-beta-1-induced NPDFs, simvastatin significantly inhibited the expressions of α-SMA and collagen type IV mRNA and reduced alpha-SMA and collagen protein levels. Pretreatment with mevalonate reversed the effect of simvastatin. The expression of alpha-SMA mRNA and protein was significantly decreased by pretreatment with Y-27632. The TGF-beta-1-induced expression of pSmad 2/3 protein was notably decreased by pretreatment with simvastatin. Conclusion: We showed that simvastatin inhibits TGF-beta-1-induced myofibroblast differentiation (expression of alpha-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.",
author = "Park, {Il Ho} and Park, {Se Jin} and Cho, {Jung Sun} and Moon, {You Mi} and Moon, {Jun Hyeok} and Tae-Hoon Kim and Lee, {Sang Hag} and Lee, {Heung Man}",
year = "2012",
month = "1",
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doi = "10.2500/ajra.2012.26.3679",
language = "English",
volume = "26",
pages = "7--11",
journal = "American Journal of Rhinology and Allergy",
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TY - JOUR

T1 - Effect of simvastatin on transforming growth factor beta-1-induced myofibroblast differentiation and collagen production in nasal polyp-derived fibroblasts

AU - Park, Il Ho

AU - Park, Se Jin

AU - Cho, Jung Sun

AU - Moon, You Mi

AU - Moon, Jun Hyeok

AU - Kim, Tae-Hoon

AU - Lee, Sang Hag

AU - Lee, Heung Man

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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 antifibrotic properties. The purpose of this study was to determine the effect of simvastatin on transforming growth factor (TGF)-beta-1-induced myofibroblast differentiation and collagen production in nasal polyp- derived fibroblasts (NPDFs) and to verify the mechanism of the effect of simvastatin in TGF-beta-1-induced myofibroblast differentiation in NPDFs. Methods: NPDFs were pretreated with simvastatin with or without mevalonate or Y-27643 for 2 hours before induction by TGF-beta-1. The expression of alpha-smooth muscle actin (SMA) and collagen type IV mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of alpha-SMA protein was determined by immunofluorescent cytochemical staining. Total soluble collagen production was analyzed by the SirCol collagen dye-binding assay (Biocolor, Belfast, U.K.). Phosphorylation of Smad 2/3 was evaluated by Western blot analysis. Results: In TGF-beta-1-induced NPDFs, simvastatin significantly inhibited the expressions of α-SMA and collagen type IV mRNA and reduced alpha-SMA and collagen protein levels. Pretreatment with mevalonate reversed the effect of simvastatin. The expression of alpha-SMA mRNA and protein was significantly decreased by pretreatment with Y-27632. The TGF-beta-1-induced expression of pSmad 2/3 protein was notably decreased by pretreatment with simvastatin. Conclusion: We showed that simvastatin inhibits TGF-beta-1-induced myofibroblast differentiation (expression of alpha-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.

AB - 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 antifibrotic properties. The purpose of this study was to determine the effect of simvastatin on transforming growth factor (TGF)-beta-1-induced myofibroblast differentiation and collagen production in nasal polyp- derived fibroblasts (NPDFs) and to verify the mechanism of the effect of simvastatin in TGF-beta-1-induced myofibroblast differentiation in NPDFs. Methods: NPDFs were pretreated with simvastatin with or without mevalonate or Y-27643 for 2 hours before induction by TGF-beta-1. The expression of alpha-smooth muscle actin (SMA) and collagen type IV mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of alpha-SMA protein was determined by immunofluorescent cytochemical staining. Total soluble collagen production was analyzed by the SirCol collagen dye-binding assay (Biocolor, Belfast, U.K.). Phosphorylation of Smad 2/3 was evaluated by Western blot analysis. Results: In TGF-beta-1-induced NPDFs, simvastatin significantly inhibited the expressions of α-SMA and collagen type IV mRNA and reduced alpha-SMA and collagen protein levels. Pretreatment with mevalonate reversed the effect of simvastatin. The expression of alpha-SMA mRNA and protein was significantly decreased by pretreatment with Y-27632. The TGF-beta-1-induced expression of pSmad 2/3 protein was notably decreased by pretreatment with simvastatin. Conclusion: We showed that simvastatin inhibits TGF-beta-1-induced myofibroblast differentiation (expression of alpha-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.

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