A Drosophila model of cigarette smoke induced COPD identifies Nrf2 signaling as an expedient target for intervention

Aging
Ruben PrangeThomas Roeder

Abstract

Chronic obstructive pulmonary disease (COPD) is among the most important causes of death. Signaling systems that are relevant for tissue repair and detoxification of reactive oxygen species or xenobiotics are thought to be impaired in lungs of patients suffering from this disease. Here, we developed a simple cigarette smoke induced Drosophila model of COPD based on chronic cigarette smoke exposure that recapitulates major pathological hallmarks of the disease and thus can be used to investigate new therapeutic strategies. Chronic cigarette smoke exposure led to premature death of the animals and induced a set of phenotypes reminiscent of those seen in COPD patients, including reduced physical activity, reduced body fat, increased metabolic rate and a substantial reduction of the respiratory surface. A detailed transcriptomic analysis revealed that especially the TGF-β, Nrf2 and the JAK/STAT signaling pathways are altered by chronic cigarette smoke exposure. Based on these results, we focused on Nrf2 signaling. A pharmacological intervention study performed with oltipraz, an activator of Nrf2 signaling, increased survival of cigarette smoke exposed animals significantly. Thus, the Drosophila COPD model recapitulates many major h...Continue Reading

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Citations

Jun 21, 2019·Molecular Cancer Therapeutics·Judith BossenThomas Roeder
Nov 12, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jennifer M K NguyenVenkataramana K Sidhaye
Feb 26, 2021·Scientific Reports·Natalia El-MerhieSusanne Krauss-Etschmann
Apr 30, 2021·Frontiers in Cardiovascular Medicine·Srikanth KarnatiSüleyman Ergün
Dec 9, 2021·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Erasmia RoukaSotirios G Zarogiannis

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Methods Mentioned

BETA
transgenic
RNAseq

Software Mentioned

TopHat
NeuronJ
cutadapt
Bioconductor
DESeq2
DAM File scan
Pscan
ImageJ
htseq
DAVID

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