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Di-tyrosine crosslinking and NOX4 expression as oxidative pathological markers in the lungs of patients with idiopathic pulmonary fibrosis

Published inAntioxidants, vol. 10, no. 11, 1833
Publication date2021-11-18
First online date2021-11-18
Abstract

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-generating enzyme NADPH oxidase 4 (NOX4) and di-tyrosine (DT), an oxidative post-translational modification in IPF lungs. We performed immunohistochemical staining for DT andNOX4in pulmonary tissue from patients with IPF and controls using validated antibodies. In the healthy lung, DT showed little or no staining andNOX4was 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 betweenNOX4and DT was addressed in human fibroblasts deficient forNOX4activity (mutation in theCYBAgene). Induction ofNOX4by 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 forNOX4activity. Our data indicate that DT is a histological marker of IPF and thatNOX4can generate a sufficient amount of H2O2for DT formation in vitro.

eng
Keywords
  • NADPH oxidase
  • NOX4
  • Di-tyrosine
  • Human lung tissue
  • Idiopathic pulmonary fibrosis
  • Immunohistochemistry
Citation (ISO format)
BLASKOVIC, Sanja et al. Di-tyrosine crosslinking and NOX4 expression as oxidative pathological markers in the lungs of patients with idiopathic pulmonary fibrosis. In: Antioxidants, 2021, vol. 10, n° 11, p. 1833. doi: 10.3390/antiox10111833
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ISSN of the journal2076-3921
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