Aberrant antioxidant activity and excessive deposition of extracellular matrix (ECM) are hallmarks of interstitial lung diseases (ILD). It is known that oxidative stress alters the ECM, but extracellular antioxidant defence mechanisms in ILD are incompletely understood. Here, we extracted abundance and detergent solubility of extracellular antioxidant enzymes from a proteomic dataset of bleomycin-induced lung fibrosis in mice and assessed regulation and distribution of glutathione peroxidase 3 (GPX3) in murine and human lung fibrosis. Superoxide dismutase 3 (Sod3), Gpx3, and Gpx activity were increased in mouse BALF during bleomycin-induced lung fibrosis. In lung tissue homogenates, Gpx3, but not Sod3, was upregulated and detergent solubility profiling indicated that Gpx3 associated with ECM proteins. Immunofluorescence analysis showed that Gpx3 was expressed by bronchial epithelial cells and interstitial fibroblasts and localized to the basement membrane and interstitial ECM in lung tissue. As to human ILD samples, BALF of some patients contained high levels of GPX3, and GPX3 was upregulated in lung homogenates from IPF patients. GPX3 expression in primary human bronchial epithelial cells and lung fibroblasts was downregulated by TNF-α, but more variably regulated by TGF-β1 and menadione. In conclusion, the antioxidant enzyme GPX3 localizes to lung ECM and is variably upregulated in ILD.

• MeSH
• antioxidancia metabolismus   MeSH
• bleomycin MeSH
• bronchoalveolární lavážní tekutina MeSH
• bronchy patologie   MeSH
• demografie MeSH
• down regulace účinky léků   MeSH
• epitelové buňky enzymologie   MeSH
• extracelulární matrix enzymologie   MeSH
• fibroblasty účinky léků   metabolismus   MeSH
• glutathionperoxidasa metabolismus   MeSH
• intersticiální plicní nemoci enzymologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• oxidační stres účinky léků   MeSH
• plicní fibróza enzymologie   MeSH
• senioři MeSH
• TNF-alfa metabolismus   MeSH
• transformující růstový faktor beta1 metabolismus   MeSH
• upregulace MeSH
• vitamin K 3 farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH