The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema

Scientific Reports
Li Hui TanBeata Kosmider

Abstract

Emphysema is characterized by irreversibly enlarged airspaces and destruction of alveolar walls. One of the factors contributing to this disease pathogenesis is an elevation in extracellular matrix (ECM) degradation in the lung. Alveolar type II (ATII) cells produce and secrete pulmonary surfactants and proliferate to restore the epithelium after damage. We isolated ATII cells from control non-smokers, smokers and patients with emphysema to determine the role of NFE2 (nuclear factor, erythroid-derived 2). NFE2 is a heterodimer composed of two subunits, a 45 kDa (p45 NFE2) and 18 kDa (p18 NFE2) polypeptides. Low expression of p45 NFE2 in patients with emphysema correlated with a high ECM degradation. Moreover, we found that NFE2 knockdown increased cell death induced by cigarette smoke extract. We also studied the cross talk between p45 NFE2 and DJ-1. DJ-1 protein is a redox-sensitive chaperone that protects cells from oxidative stress. We detected that cigarette smoke significantly increased p45 NFE2 levels in DJ-1 KO mice compared to wild-type mice. Our results indicate that p45 NFE2 expression is induced by exposure to cigarette smoke, has a cytoprotective activity against cell injury, and its downregulation in human primary ...Continue Reading

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Citations

Jul 18, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Chih-Ru LinBeata Kosmider
Jan 31, 2019·Scientific Reports·Beata KosmiderKarim Bahmed
Jul 18, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Karim BahmedBeata Kosmider

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Methods Mentioned

BETA
immunoprecipitation
flow cytometry
bronchoalveolar lavage
transfection

Software Mentioned

TreeStar
ImageJ
NIH Image
Zeiss Axio Imager
FlowJo

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