1. The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema.
- Author
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Tan LH, Bahmed K, Lin CR, Marchetti N, Bolla S, Criner GJ, Kelsen S, Madesh M, and Kosmider B
- Subjects
- Animals, Cell Proliferation genetics, Cigarette Smoking adverse effects, Emphysema physiopathology, Extracellular Matrix genetics, Extracellular Matrix metabolism, Gene Expression Regulation drug effects, Humans, Lung metabolism, Lung physiopathology, Mice, Knockout, Pulmonary Alveoli metabolism, Pulmonary Alveoli physiopathology, Emphysema genetics, Lung drug effects, NF-E2 Transcription Factor, p45 Subunit genetics, Protein Deglycase DJ-1 genetics
- 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 ATII cells may contribute to emphysema pathogenesis.
- Published
- 2018
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