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
• Antioxidants metabolism   MeSH
• Bleomycin MeSH
• Bronchoalveolar Lavage Fluid MeSH
• Bronchi pathology   MeSH
• Demography MeSH
• Down-Regulation drug effects   MeSH
• Epithelial Cells enzymology   MeSH
• Extracellular Matrix enzymology   MeSH
• Fibroblasts drug effects   metabolism   MeSH
• Glutathione Peroxidase metabolism   MeSH
• Lung Diseases, Interstitial enzymology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Mice, Inbred C57BL MeSH
• Oxidative Stress drug effects   MeSH
• Pulmonary Fibrosis enzymology   MeSH
• Aged MeSH
• Tumor Necrosis Factor-alpha metabolism   MeSH
• Transforming Growth Factor beta1 metabolism   MeSH
• Up-Regulation MeSH
• Vitamin K 3 pharmacology   MeSH
• Animals MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antioxidants MeSH
• Bleomycin MeSH
• Glutathione Peroxidase MeSH
• GPX3 protein, human MeSH Browser
• Gpx3 protein, mouse MeSH Browser
• Tumor Necrosis Factor-alpha MeSH
• Transforming Growth Factor beta1 MeSH
• Vitamin K 3 MeSH