Di-Tyrosine Crosslinking and NOX4 Expression as Oxidative Pathological Markers in the Lungs of Patients with Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a noninflammatory progressive lung disease. Oxidative damage is a hallmark of IPF, but the sources and consequences of oxidant generation in the lungs are unclear. In this study, we addressed the link between the H2O2</sub&g...

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Autores principales:	Sanja Blaskovic, Yves Donati, Isabelle Ruchonnet-Metrailler, Tamara Seredenina, Karl-Heinz Krause, Jean-Claude Pache, Dan Adler, Constance Barazzone-Argiroffo, Vincent Jaquet
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	idiopathic pulmonary fibrosis NADPH oxidase <i>NOX4</i> di-tyrosine immunohistochemistry human lung tissue Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/e4be938dd67342a1870aef9678a650fd
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spelling	oai:doaj.org-article:e4be938dd67342a1870aef9678a650fd2021-11-25T16:29:27ZDi-Tyrosine Crosslinking and <i>NOX4</i> Expression as Oxidative Pathological Markers in the Lungs of Patients with Idiopathic Pulmonary Fibrosis10.3390/antiox101118332076-3921https://doaj.org/article/e4be938dd67342a1870aef9678a650fd2021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1833https://doaj.org/toc/2076-3921Idiopathic pulmonary fibrosis (IPF) is a noninflammatory progressive lung disease. Oxidative damage is a hallmark of IPF, but the sources and consequences of oxidant generation in the lungs are unclear. In this study, we addressed the link between the H<sub>2</sub>O<sub>2</sub>-generating enzyme NADPH oxidase 4 (<i>NOX4</i>) and di-tyrosine (DT), an oxidative post-translational modification in IPF lungs. We performed immunohistochemical staining for DT and <i>NOX4</i> in pulmonary tissue from patients with IPF and controls using validated antibodies. In the healthy lung, DT showed little or no staining and <i>NOX4</i> was mostly present in normal vascular endothelium. On the other hand, both markers were detected in several cell types in the IPF patients, including vascular smooth muscle cells and epithelium (bronchial cells and epithelial cells type II). The link between <i>NOX4</i> and DT was addressed in human fibroblasts deficient for <i>NOX4</i> activity (mutation in the <i>CYBA</i> gene). Induction of <i>NOX4</i> by Transforming growth factor beta 1 (TGFβ1) in fibroblasts led to moderate DT staining after the addition of a heme-containing peroxidase in control cells but not in the fibroblasts deficient for <i>NOX4</i> activity. Our data indicate that DT is a histological marker of IPF and that <i>NOX4</i> can generate a sufficient amount of H<sub>2</sub>O<sub>2</sub> for DT formation in vitro.Sanja BlaskovicYves DonatiIsabelle Ruchonnet-MetraillerTamara SeredeninaKarl-Heinz KrauseJean-Claude PacheDan AdlerConstance Barazzone-ArgiroffoVincent JaquetMDPI AGarticleidiopathic pulmonary fibrosisNADPH oxidase<i>NOX4</i>di-tyrosineimmunohistochemistryhuman lung tissueTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1833, p 1833 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	idiopathic pulmonary fibrosis NADPH oxidase <i>NOX4</i> di-tyrosine immunohistochemistry human lung tissue Therapeutics. Pharmacology RM1-950
spellingShingle	idiopathic pulmonary fibrosis NADPH oxidase <i>NOX4</i> di-tyrosine immunohistochemistry human lung tissue Therapeutics. Pharmacology RM1-950 Sanja Blaskovic Yves Donati Isabelle Ruchonnet-Metrailler Tamara Seredenina Karl-Heinz Krause Jean-Claude Pache Dan Adler Constance Barazzone-Argiroffo Vincent Jaquet Di-Tyrosine Crosslinking and <i>NOX4</i> Expression as Oxidative Pathological Markers in the Lungs of Patients with Idiopathic Pulmonary Fibrosis
description	Idiopathic pulmonary fibrosis (IPF) is a noninflammatory progressive lung disease. Oxidative damage is a hallmark of IPF, but the sources and consequences of oxidant generation in the lungs are unclear. In this study, we addressed the link between the H<sub>2</sub>O<sub>2</sub>-generating enzyme NADPH oxidase 4 (<i>NOX4</i>) and di-tyrosine (DT), an oxidative post-translational modification in IPF lungs. We performed immunohistochemical staining for DT and <i>NOX4</i> in pulmonary tissue from patients with IPF and controls using validated antibodies. In the healthy lung, DT showed little or no staining and <i>NOX4</i> was mostly present in normal vascular endothelium. On the other hand, both markers were detected in several cell types in the IPF patients, including vascular smooth muscle cells and epithelium (bronchial cells and epithelial cells type II). The link between <i>NOX4</i> and DT was addressed in human fibroblasts deficient for <i>NOX4</i> activity (mutation in the <i>CYBA</i> gene). Induction of <i>NOX4</i> by Transforming growth factor beta 1 (TGFβ1) in fibroblasts led to moderate DT staining after the addition of a heme-containing peroxidase in control cells but not in the fibroblasts deficient for <i>NOX4</i> activity. Our data indicate that DT is a histological marker of IPF and that <i>NOX4</i> can generate a sufficient amount of H<sub>2</sub>O<sub>2</sub> for DT formation in vitro.
format	article
author	Sanja Blaskovic Yves Donati Isabelle Ruchonnet-Metrailler Tamara Seredenina Karl-Heinz Krause Jean-Claude Pache Dan Adler Constance Barazzone-Argiroffo Vincent Jaquet
author_facet	Sanja Blaskovic Yves Donati Isabelle Ruchonnet-Metrailler Tamara Seredenina Karl-Heinz Krause Jean-Claude Pache Dan Adler Constance Barazzone-Argiroffo Vincent Jaquet
author_sort	Sanja Blaskovic
title	Di-Tyrosine Crosslinking and <i>NOX4</i> Expression as Oxidative Pathological Markers in the Lungs of Patients with Idiopathic Pulmonary Fibrosis
title_short	Di-Tyrosine Crosslinking and <i>NOX4</i> Expression as Oxidative Pathological Markers in the Lungs of Patients with Idiopathic Pulmonary Fibrosis
title_full	Di-Tyrosine Crosslinking and <i>NOX4</i> Expression as Oxidative Pathological Markers in the Lungs of Patients with Idiopathic Pulmonary Fibrosis
title_fullStr	Di-Tyrosine Crosslinking and <i>NOX4</i> Expression as Oxidative Pathological Markers in the Lungs of Patients with Idiopathic Pulmonary Fibrosis
title_full_unstemmed	Di-Tyrosine Crosslinking and <i>NOX4</i> Expression as Oxidative Pathological Markers in the Lungs of Patients with Idiopathic Pulmonary Fibrosis
title_sort	di-tyrosine crosslinking and <i>nox4</i> expression as oxidative pathological markers in the lungs of patients with idiopathic pulmonary fibrosis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e4be938dd67342a1870aef9678a650fd
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Di-Tyrosine Crosslinking and <i>NOX4</i> Expression as Oxidative Pathological Markers in the Lungs of Patients with Idiopathic Pulmonary Fibrosis

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