Cigarette Smoke Exposure in Drosophila Reveals Wnt-Mediated Remodeling of Airway Structure and Systemic Physiology

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by irreversible airflow limitation, chronic inflammation, epithelial injury, and impaired tissue repair, with cigarette smoke as its primary etiological factor. Increasing evidence implicates dysregulation of the Wnt signaling pathway in COPD pathogenesis, yet the distinct roles of canonical and non-canonical Wnt signaling in smoke-induced airway injury remain incompletely understood. In this study, a chronic cigarette smoke–exposed Drosophila melanogaster model was established to investigate the role of Wnt signaling in airway epithelial homeostasis. Chronic smoke exposure in Drosophila resulted in reduced developmental success, shortened lifespan, impaired locomotor activity, metabolic imbalance, increased apoptosis of tracheal epithelial cells, and disrupted tracheal architecture. Using tracheal-specific genetic manipulations, we systematically examined the effects of canonical Wnt/β-catenin signaling and non-canonical Wnt signaling mediated by the Rho GTPases Rho1 and Rac1. Activation of canonical Wnt signaling through β-catenin overexpression significantly alleviated smoke-induced defects, improving developmental rates, survival, locomotor performance, and metabolic balance. At the cellular level, β-catenin activation reduced tracheal epithelial apoptosis during development and preserved the number and organization of terminal tracheal cells in adults. Conversely, excessive activation of non-canonical Wnt signaling increased airway vulnerability. Tracheal overexpression of Rho1 or Rac1 impaired development and survival, induced metabolic dysregulation with increased fat accumulation, and caused pronounced structural abnormalities in the tracheal system. In summary, this study demonstrates that airway resilience to cigarette smoke is governed by the balance between protective canonical Wnt/β-catenin signaling and detrimental overactivation of non-canonical Rho GTPase pathways. Disruption of this balance promotes epithelial apoptosis, structural degeneration, and functional decline, providing mechanistic insight into smoke-induced airway injury and identifying conserved molecular targets relevant to COPD pathogenesis.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Christian-Albrechts-Universität zu Kiel

Year

2026

Author dc:creator

• Yang, Liu

Contributors dc:contributor

• Roeder, Thomas
• Heine, Holger

• Drosophila
• COPD
• Wnt pathway

Repository record source_url

https://macau.uni-kiel.de/receive/macau_mods_00008752

OAI identifier oai:identifier

oai:macau.uni-kiel.de:macau_mods_00008752