NOX4/NADPH oxidase expression is increased in pulmonary fibroblasts from patients with idiopathic pulmonary fibrosis and mediates TGFbeta1-induced fibroblast differentiation into myofibroblasts
| العنوان: | NOX4/NADPH oxidase expression is increased in pulmonary fibroblasts from patients with idiopathic pulmonary fibrosis and mediates TGFbeta1-induced fibroblast differentiation into myofibroblasts |
|---|---|
| المؤلفون: | Amara, Nadia, Goven, Delphine, Prost, Fabienne, Muloway, Rachel, Crestani, Bruno, Boczkowski, Jorge |
| المساهمون: | Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pneumologie A, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de physiologie, explorations fonctionnelles [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de pneumologie et pathologie professionnelle, CHI Créteil, Nadia Amara was supported by Chancellerie des Universités de Paris (legs Poix), and Jorge Boczkowski by INSERM and Assistance Publique-Hôpitaux de Paris (Contrat d'Interface). This work was supported by the European Commission (FP 7, European IPF Network) and by the Agence Nationale de la Recherche (ANR Physio 2006, FIBROPNEUMO)., ANR-06-PHYS-0011,FIBROPNEUMO,Fibroblastes et Fibrogénèse pulmonaire(2006), European Project: 202224,EC:FP7:HEALTH,FP7-HEALTH-2007-A,EURIPFNET(2008) |
| المصدر: | Thorax Thorax, BMJ Publishing Group, 2010, 65 (8), pp.733-8. ⟨10.1136/thx.2009.113456⟩ |
| بيانات النشر: | HAL CCSD, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | MESH: Aged, MESH: Cell Differentiation, MESH: Middle Aged, MESH: Humans, MESH: Gene Expression Regulation, Enzymologic, MESH: Idiopathic Pulmonary Fibrosis, MESH: Platelet-Derived Growth Factor, MESH: Reactive Oxygen Species, MESH: Adult, MESH: Male, MESH: Transforming Growth Factor beta1, MESH: Fibroblasts, MESH: Reverse Transcriptase Polymerase Chain Reaction, cardiovascular system, MESH: Up-Regulation, MESH: Smad3 Protein, MESH: Lung, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: NADPH Oxidase, MESH: Smad2 Protein, MESH: Female, MESH: RNA, Messenger, MESH: Cells, Cultured |
| الوصف: | International audience; 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. |
| اللغة: | English |
| تدمد: | 0040-6376 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::305a40964b64aca53decb6ac483387ce https://www.hal.inserm.fr/inserm-00515220 |
| رقم الأكسشن: | edsair.dedup.wf.001..305a40964b64aca53decb6ac483387ce |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00406376 |
|---|