{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:51:52Z","timestamp":1789876312465,"version":"4.0.1"},"reference-count":34,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss national science foundation","doi-asserted-by":"publisher","award":["310030-159500\/1"],"award-info":[{"award-number":["310030-159500\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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 and NOX4 in pulmonary tissue from patients with IPF and controls using validated antibodies. In the healthy lung, DT showed little or no staining and NOX4 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 NOX4 and DT was addressed in human fibroblasts deficient for NOX4 activity (mutation in the CYBA gene). Induction of NOX4 by Transforming growth factor beta 1 (TGF\u03b21) 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 NOX4 activity. Our data indicate that DT is a histological marker of IPF and that NOX4 can generate a sufficient amount of H2O2 for DT formation in vitro.<\/jats:p>","DOI":"10.3390\/antiox10111833","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T02:43:09Z","timestamp":1637289789000},"page":"1833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Di-Tyrosine Crosslinking and NOX4 Expression as Oxidative Pathological Markers in the Lungs of Patients with Idiopathic Pulmonary Fibrosis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4399-3271","authenticated-orcid":false,"given":"Sanja","family":"Blaskovic","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Gynecology and Obstetrics, Children\u2019s Hospital, 1211 Geneva, Switzerland"},{"name":"Department of Pathology and Immunology, Medical School, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Donati","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Gynecology and Obstetrics, Children\u2019s Hospital, 1211 Geneva, Switzerland"},{"name":"Department of Pathology and Immunology, Medical School, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4771-875X","authenticated-orcid":false,"given":"Isabelle","family":"Ruchonnet-Metrailler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Gynecology and Obstetrics, Children\u2019s Hospital, 1211 Geneva, Switzerland"},{"name":"Department of Pathology and Immunology, Medical School, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Seredenina","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Medical School, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9033-6768","authenticated-orcid":false,"given":"Karl-Heinz","family":"Krause","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Medical School, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Claude","family":"Pache","sequence":"additional","affiliation":[{"name":"Service of Clinical Pathology, Department of Pathology and Immunology, Medical School, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9915-862X","authenticated-orcid":false,"given":"Dan","family":"Adler","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Diseases, Department of Medicine, Geneva University Hospitals, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constance","family":"Barazzone-Argiroffo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Gynecology and Obstetrics, Children\u2019s Hospital, 1211 Geneva, Switzerland"},{"name":"Department of Pathology and Immunology, Medical School, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Jaquet","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Medical School, University of Geneva, 1211 Geneva, Switzerland"},{"name":"READS Unit, Medical School, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1146\/annurev-pathol-012513-104706","article-title":"Pathogenesis of Idiopathic Pulmonary Fibrosis","volume":"9","author":"Wolters","year":"2014","journal-title":"Annu. 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