Pneumologie 2016; 70 - P5
DOI: 10.1055/s-0036-1584608

Dysregulation of epithelial JAK/STAT-signaling leads to malformation of the fruit fly's airways

C Fink 1, K Kallsen 2, A Bhandari 1, T Roeder 1
  • 1Molecular Physiology, Zoological Institute, Christian-Albrechts-University Kiel, Kiel
  • 2Research Center Borstel, Borstel

Worldwide, many hundred million people suffer from chronic respiratory diseases like COPD, pulmonary hypertension and asthma. Beside genetic predisposition there are many risk factors like allergens, tobacco smoke and air pollution that may promote development of asthma. However, the signaling components relevant for pathogenesis are not yet fully understood. Key members of the evolutionary highly conserved JAK/STAT pathway (STAT3/6) are known to mediate susceptibility to asthma.

We used Drosophila melanogaster to analyze the role of JAK/STAT signaling in the fly's airway epithelium under different stress conditions including oxidative stress, UV radiation and hypoxia. Furthermore, we investigated if and how the endogenous ligands of the JAK/STAT signaling (upd ligands) are regulated and if their enhanced expression leads to structural changes of the airways epithelia.

Our results illustrate a time dependent expression of the ligands upd2 and upd3 in oxygen undersupplied wildtype flies and therewith an autocrine activation of JAK/STAT signaling. Furthermore, we observed structural changes due to ectopic overexpression of upd ligands in the whole tracheal system. We could detect a dramatic increase in epithelial plasticity as represented by epithelial thickening of the dorsal trunks. Additionally, we were able to show that Wnt signaling is downstream of JAK/STAT signaling, which is presumably responsible for the structurally damaged epithelium.

JAK/STAT appears to be a key factor in maintaining the epithelial homeostasis of the fruit fly's respiratory system, highlighting that carriers of susceptible alleles (STAT3/6) may be prone to develop structural changes of their airways relevant for disease development.