Role of reactive oxygen species in transforming growth factor beta1-induced alpha smooth-muscle actin and collagen production in nasal polyp-derived fibroblasts

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Myofibroblasts are detected in nasal polyps and are involved in nasal polyp formation by inducing extracellular matrix accumulation. Reactive oxygen species (ROS) are released during the differentiation of fibroblasts to myofibroblasts. The purpose of this study was to investigate ROS production and nicotinamide adenine dinucleotide phosphate oxidase (NOX) expression in nasal polyp-derived fibroblasts (NPDFs) and to evaluate whether ROS from NOX mediates transforming growth factor (TGF)-β1-induced production of alpha smooth-muscle actin (α-SMA) and collagen production. Methods: NPDFs were incubated and treated with TGF-β1. The mRNA expression of NOXs, α-SMA, and collagen type I and IV was determined by reverse transcription-polymerase chain reaction, and the expression of α-SMA protein was determined by immunofluorescence microscopy. The amount of total soluble collagen production was analyzed by the SirCol assay. The ROS generation of cells was investigated using the 2′,7′-dichlorfluorescein- diacetate. The fluorescence was captured by fluorescent microscope and measured using a fluorometer. Results: Stimulation with TGF-β1 increased ROS production by NPDFs compared with NPDFs not treated with TGF-β1. Stimulation with TGF-β1 increased the expression of NOX4 mRNA most potently among various Nox enzymes. siNOX4 was able to decrease the level of ROS production. Myofibroblast differentiation and the production of collagen in NPDFs were prevented by inhibition of ROS generation with diphenyliodonium, N-acetylcysteine, ebselen, and siNox4. Conclusions: This study showed that NOX4 and ROS have a role in myofibroblast differentiation and collagen production of TGF-β1-induced NPDFs and that these processes are inhibited by the elimination of ROS.

Original languageEnglish
Pages (from-to)278-286
Number of pages9
JournalInternational Archives of Allergy and Immunology
Volume159
Issue number3
DOIs
Publication statusPublished - 2012 Oct 1

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Keywords

  • Alpha-smooth-muscle actin
  • Myofibroblast
  • Nasal polyps
  • Nicotinamide adenine dinucleotide phosphate oxidase
  • Reactive oxygen species
  • Transforming growth factor-beta1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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