ORMDL deregulation increases stress responses and modulates repair pathways in Drosophila airways

Kallsen, Kimberley; Zehethofer, Nicole; Abdelsadik, Ahmed; Lindner, Buko; Kabesch, Michael; Heine, Holger; Roeder, Thomas

doi:10.1016/j.jaci.2015.04.009

Cited by 18 publications

(16 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to evaluate if the activity of the corresponding pathways were indeed induced or impaired, we analyzed either canonical pathway genes of these pathways or essential pathway constituents by qRT-PCR. For the MAPK/EGFR-pathway, expression of the canonical pathway gene spitz 29 was upregulated several fold (*p < 0.05; Fig. 3C ).…”

Section: Resultsmentioning

confidence: 99%

Impaired Wnt signaling in dopamine containing neurons is associated with pathogenesis in a rotenone triggered Drosophila Parkinson’s disease model

Stephano

Nolte

Hoffmann

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

Parkinson’s disease, which is the one of the most common neurodegenerative movement disorder, is characterized by a progressive loss of dopamine containing neurons. The mechanisms underlying disease initiation and development are not well understood and causative therapies are currently not available. To elucidate the molecular processes during early stages of Parkinson’s disease, we utilized a Drosophila model. To induce Parkinson’s disease-like phenotypes, we treated flies with the pesticide rotenone and isolated dopamine producing neurons of animals that were at an early disease stage. Transcriptomic analyses revealed that gene ontologies associated with regulation of cell death and neuronal functions were significantly enriched. Moreover, the activities of the MAPK/EGFR- and TGF-β signaling pathways were enhanced, while the Wnt pathway was dampened. In order to evaluate the role of Wnt signaling for survival of dopaminergic neurons in the disease model, we rescued the reduced Wnt signaling activity by ectopic overexpression of armadillo/β-catenin. This intervention rescued the rotenone induced movement impairments in the Drosophila model. Taken together, this initial study showed a highly relevant role of Wnt signaling for dopamine producing neurons during pathogenesis in Parkinson’s disease and it implies that interfering with this pathway might by a suitable therapeutic option for the future.

show abstract

Section: Resultsmentioning

confidence: 99%

Impaired Wnt signaling in dopamine containing neurons is associated with pathogenesis in a rotenone triggered Drosophila Parkinson’s disease model

Stephano

Nolte

Hoffmann

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…For the gene expression analysis of 3 rd instar larvae trachea, larvae were dissected in cold PBS and transferred to RNA Magic (BioBudget, Krefeld, Germany) and processed essentially as described earlier [ 23 ] with slight modifications. The tissue was homogenized in a Bead Ruptor 24 (BioLab products, Bebensee, Germany) and the RNA was extracted by using the PureLink RNA Mini Kit (Thermo Fisher, Waltham, MA, USA) for phase separation with the RNA Magic reagent.…”

Section: Methodsmentioning

confidence: 99%

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

Prange

Thiedmann

Bhandari

et al. 2018

Aging

Self Cite

View full text Add to dashboard Cite

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 hallmarks of COPD and it is highly useful to evaluate the potential of alternative therapeutic strategies.

show abstract

“…Polymorphisms in this gene are strongly associated with childhood asthma . The authors showed that enhanced epithelial expression of the Drosophila ORDML homologue reduces the ability of adult flies to cope with asthma risk factors such as cigarette smoke …”

Section: Drosophila Melanogastermentioning

confidence: 99%

In utero exposure to cigarette smoke and effects across generations: A conference of animals on asthma

Hammer

Wagner

Rankov

et al. 2018

Clin Experimental Allergy

View full text Add to dashboard Cite

Summary Background The prevalence of asthma and chronic obstructive pulmonary disease (COPD) has risen markedly over the last decades and is reaching epidemic proportions. However, underlying molecular mechanisms are not fully understood, hampering the urgently needed development of approaches to prevent these diseases. It is well established from epidemiological studies that prenatal exposure to cigarette smoke is one of the main risk factors for aberrant lung function development or reduced fetal growth, but also for the development of asthma and possibly COPD later in life. Of note, recent evidence suggests that the disease risk can be transferred across generations, that is, from grandparents to their grandchildren. While initial studies in mouse models on in utero smoke exposure have provided important mechanistic insights, there are still knowledge gaps that need to be filled. Objective Thus, in this review, we summarize current knowledge on this topic derived from mouse models, while also introducing two other relevant animal models: the fruit fly Drosophila melanogaster and the zebrafish Danio rerio. Methods This review is based on an intensive review of PubMed‐listed transgenerational animal studies from 1902 to 2018 and focuses in detail on selected literature due to space limitations. Results This review gives a comprehensive overview of mechanistic insights obtained in studies with the three species, while highlighting the remaining knowledge gaps. We will further discuss potential (dis)advantages of all three animal models. Conclusion/Clinical Relevance Many studies have already addressed transgenerational inheritance of disease risk in mouse, zebrafish or fly models. We here propose a novel strategy for how these three model organisms can be synergistically combined to achieve a more detailed understanding of in utero cigarette smoke‐induced transgenerational inheritance of disease risk.

show abstract

ORMDL deregulation increases stress responses and modulates repair pathways in Drosophila airways

Cited by 18 publications

References 8 publications

Impaired Wnt signaling in dopamine containing neurons is associated with pathogenesis in a rotenone triggered Drosophila Parkinson’s disease model

Impaired Wnt signaling in dopamine containing neurons is associated with pathogenesis in a rotenone triggered Drosophila Parkinson’s disease model

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

In utero exposure to cigarette smoke and effects across generations: A conference of animals on asthma

Contact Info

Product

Resources

About