Cell-specific elevation of NRF2 and sulfiredoxin-1 as markers of oxidative stress in the lungs of idiopathic pulmonary fibrosis and non-specific interstitial pneumonia.
Human idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) have been proposed to be attributable to oxidative stress. The nuclear factor, erythroid derived 2, like protein (NRF2)-sulfiredoxin-1 (SRX1) pathway was hypothesized to be associated with the pathogenesis of human pulmonary fibrosis. Several methods including digital morphometry were used in the assessment of the cell-specific localization and expression of NRF2 and SRX1 and selected proteins linked to their activation/stability in human IPF/usual interstitial pneumonia (UIP) and NSIP lung. The proteins of the NRF2 pathway were localized in the hyperplastic alveolar epithelium and inflammatory cells in IPF and NSIP, but were absent in the fibroblastic foci characteristic of IPF. Morphometric evaluation revealed NRF2 and KEAP1 to be significantly elevated in the hyperplastic alveolar epithelium compared with the normal alveolar epithelium, and NRF2 was remarkably expressed in the nuclear compartment of the hyperplastic cells. SRX1 was expressed mainly in alveolar macrophages, and the number of SRX1-positive macrophages/surface area was elevated in NSIP, a disease which contains more marked inflammatory reaction compared with the IPF/UIP lung. The expression of the NRF2 pathway in human IPF and NSIP is further evidence that the pathogenesis of human fibrotic lung diseases is oxidant-mediated and originates from the alveolar epithelium.
Mazur
Witold
W
Department of Medicine, University of Helsinki, Helsinki University Hospital, Finland.
Lindholm
Pamela
P
Vuorinen
Kirsi
K
Myllärniemi
Marjukka
M
Salmenkivi
Kaisa
K
Kinnula
Vuokko L
VL
D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006222:Hamartoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D008168:Lung / Q000378:metabolism*; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism; D018384:Oxidative Stress; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D014797:Vital Capacity
D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D015513:Oncogene Proteins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C504024:SRXN1 protein, human; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1