Smoking p66Shc knocked out mice develop respiratory bronchiolitis with fibrosis but not emphysema

PloS One
Benedetta LunghiMonica Lucattelli

Abstract

The adaptor protein p66Shc regulates intracellular oxidant levels through the modulation of a forkhead-related transcription factor (FOXO3a). The genetic ablation of p66Shc (p66Shc-/-) renders mice resistant to oxidative stress and p53-dependent apoptosis. We investigated whether p66Shc ablation in mice modifies lung cellular and molecular responses to cigarette smoke (CS) exposure. No differences between wild type (WT) and p66Shc-/- mice were observed in terms of inflammation and oxidant burden after acute CS exposure; however,p66Shc ablation modifies specific features of chronic inflammation induced by repeated exposure to CS. Unlike WT mice, p66Shc-/- mice did not develop emphysema, showing protection toward oxidative damage to DNA and apoptosis as revealed by a trivial 8-hydroxyguanosine staining and faint TUNEL and caspase-3 positivity on alveolar epithelial cells. Unexpectedly, CS exposure in p66Shc-/- mice resulted in respiratory bronchiolitis with fibrosis in surrounded alveoli. Respiratory bronchiolitis was characterized by peribronchiolar infiltrates of lymphocytes and histiocytes, accumulation of ageing pigmented macrophages within and around bronchioles, and peribronchiolar fibrosis. The blockage of apoptosis interf...Continue Reading

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Citations

Nov 3, 2015·Current Protocols in Toxicology·Mariusz R WieckowskiPaulo J Oliveira
Feb 19, 2020·Journal of Translational Medicine·Daojuan WangYong Wang
Apr 21, 2020·International Journal of Nanomedicine·Hyo Jung ShinDong Woon Kim
Jul 28, 2020·Investigative Ophthalmology & Visual Science·Gian Marco TosiEugenio Bertelli
Jun 18, 2020·International Journal of Chronic Obstructive Pulmonary Disease·Giovanna De CuntoGiuseppe Lungarella

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Methods Mentioned

BETA
Assay
bronchoalveolar lavage
ELISA
electrophoresis
PCR
targeted mutation
light microscopy

Software Mentioned

ProbeFinder

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