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Prange, R.* ; Thiedmann, M.* ; Bhandari, A.* ; Mishra, N.* ; Sinha, A.* ; Häsler, R.* ; Rosenstiel, P.* ; Uliczka, K.* ; Wagner, C.* ; Yildirim, A.Ö. ; Fink, C.* ; Roeder, T.*

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

Aging 10, 2122-2135 (2018)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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-beta, 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 hallmarks of COPD and it is highly useful to evaluate the potential of alternative therapeutic strategies.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Aging ; Life Span ; Cigarette Smoke ; Copd ; Oltipraz; Obstructive Pulmonary-disease; Extend Life-span; Animal-models; Oxidative Stress; Gene-expression; Lung-cancer; Glutathione; Emphysema; Pathway; Fly
ISSN (print) / ISBN 1945-4589
e-ISSN 1945-4589
Zeitschrift Aging
Quellenangaben Band: 10, Heft: 8, Seiten: 2122-2135 Artikelnummer: , Supplement: ,
Verlag Impact Journals LLC
Verlagsort 6666 E Quaker St, Ste 1, Orchard Park, Ny 14127 Usa
Begutachtungsstatus