Zebrafish as a model for asthma research - role of Wnt signalling in response to cigarette smoke

Principal investigator: dr Aleksandra Divac Rankov

Asthma is one of the most common chronic diseases in childhood, with increasing prevalence throughout the world. The processes underlying the development of asthma are complex and not fully understood, which is why preventative strategies and personalized therapies are lacking. Smoking represents a proven risk for development of lung diseases, and prenatal (especially grand-maternal) smoking has been linked to higher risk of developing childhood asthma. The mechanisms leading to this higher risk remain to be elucidated. Furthermore the new trend of electronic cigarette (ecig) smoking is at a rise, but their consequences are still not fully known, and warrant further investigation. It has been shown that Wnt signalling is aberrant in asthma and that there are changes in expression of beta-catenin, Frizzled-7 (Fzd-7) and fibronectin after prenatal cigarette smoke exposure. Recently, miR-142-3p has been proposed to have influence on Wnt signalling in asthma. Although some epidemiological human transgenerational studies have been performed, animal transgenerational models are used to investigate processes that can lead to development of the disease. The mouse is one of the widely used models to study asthma, but new models are emerging to study the effects of smoking, such as zebrafish and drosophila. The transgenerational effects are caused by changes in the epigenetic regulation of gene expression, due to changes in methylation, miRNA expression and other mechanisms, and smoking has been linked to all of them. We will examine effects of classical and electronic cigarettes on Wnt signalling and expression of miRNA 142-3p in zebrafish, in order to validate this model for asthma research. The main outcomes of this study will be validation of zebrafish as a model organism to study development of asthma through generations. This will also open a field of using zebrafish as a model to study therapy of asthma in future.