| NOX4/NADPH oxidase expression is increased in pulmonary fibroblasts from patients with idiopathic pulmonary fibrosis and mediates TGFbeta1-induced fibroblast differentiation into myofibroblasts. | |
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MedLine Citation:
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PMID: 20685750 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Persistence of myofibroblasts is believed to contribute to the development of fibrosis in idiopathic pulmonary fibrosis (IPF). Transforming growth factor beta1 (TGFbeta1) irreversibly converts fibroblasts into pathological myofibroblasts, which express smooth muscle alpha-actin (alpha-SMA) and produce extracellular matrix proteins, such as procollagen I (alpha1). Reactive oxygen species produced by NADPH oxidases (NOXs) have been shown to regulate cell differentiation. It was hypothesised that NOX could be expressed in parenchymal pulmonary fibroblasts and could mediate TGFbeta1-stimulated conversion of fibroblasts into myofibroblasts. METHODS: Fibroblasts were cultured from the lung of nine controls and eight patients with IPF. NOX4, alpha-SMA and procollagen I (alpha1) mRNA and protein expression, reactive oxygen species production and Smad2/3 phosphorylation were quantified, in the absence and in the presence of incubation with TGFbeta1. Migration of platelet-derived growth factor (PDGF)-induced fibroblasts was also assessed. RESULTS: It was found that (1) NOX4 mRNA and protein expression was upregulated in pulmonary fibroblasts from patients with IPF and correlated with mRNA expression of alpha-SMA and procollagen I (alpha1) mRNA; (2) TGFbeta1 upregulated NOX4, alpha-SMA and procollagen I (alpha1) expression in control and IPF fibroblasts; (3) the change in alpha-SMA and procollagen I (alpha1) expression in response to TGFbeta1 was inhibited by antioxidants and by a NOX4 small interfering RNA (siRNA); (4) NOX4 modulated alpha-SMA and procollagen I (alpha1) expression by controlling activation of Smad2/3; and (5) NOX4 modulated PDGF-induced fibroblast migration. CONCLUSION: NOX4 is critical for modulation of the pulmonary myofibroblast phenotype in IPF, probably by modulating the response to TGFbeta1 and PDGF. |
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Authors:
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Nadia Amara; Delphine Goven; Fabienne Prost; Rachel Muloway; Bruno Crestani; Jorge Boczkowski |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Thorax Volume: 65 ISSN: 1468-3296 ISO Abbreviation: Thorax Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-05 Completed Date: 2010-09-01 Revised Date: 2010-12-21 |
Medline Journal Info:
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Nlm Unique ID: 0417353 Medline TA: Thorax Country: England |
Other Details:
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Languages: eng Pagination: 733-8 Citation Subset: IM |
Affiliation:
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INSERM, Unité 700, Université Paris 7 Denis Diderot, site Bichat, Paris, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Cell Differentiation / drug effects, physiology Cells, Cultured Female Fibroblasts / drug effects, enzymology*, pathology Gene Expression Regulation, Enzymologic Humans Idiopathic Pulmonary Fibrosis / enzymology, pathology* Lung / enzymology, pathology* Male Middle Aged NADPH Oxidase / biosynthesis*, genetics, physiology Platelet-Derived Growth Factor / pharmacology RNA, Messenger / genetics Reactive Oxygen Species / metabolism Reverse Transcriptase Polymerase Chain Reaction / methods Smad2 Protein / metabolism Smad3 Protein / metabolism Transforming Growth Factor beta1 / pharmacology* Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Platelet-Derived Growth Factor; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/SMAD2 protein, human; 0/SMAD3 protein, human; 0/Smad2 Protein; 0/Smad3 Protein; 0/Transforming Growth Factor beta1; EC 1.6.3.-/NOX4 protein, human; EC 1.6.3.1/NADPH Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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