Airway epithelial cell-specific deletion of EGFR in Scnn1b transgenic mice modulates inflammatory responses but doesn’t affect muco-obstructive features of lung disease

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B230
Abstract ID: 4790

Presenting Author:
Ishita Choudhary , Post Doctoral Researcher at North Carolina State Univ. Col. of Vet. Med.

Abstract:

Epidermal growth factor receptor (EGFR) is known to regulate airway mucous cell metaplasia, but the roles of EGFR-mediated pathway in the manifestation of cystic fibrosis (CF)-relevant lung phenotypes remain unclear. We hypothesized that airway epithelial cell-specific deficiency of EGFR mitigates muco-obstructive and inflammatory responses in sodium channel, non-voltage gated 1, beta subunit (Scnn1b) overexpressing -transgenic (Tg+) mice, a mouse model of human CF-like lung disease. To test our hypothesis, we generated airway epithelial cell-specific EGFR-deficient mice and performed various endpoint analyses. The deletion of EGFR in airway epithelial cells in Tg+ mice resulted in increased neutrophilic and macrophage infiltration into lung airspaces, which was accompanied by significantly increased levels of KC, G-CSF, MIP-2, MIP-1α, and MIP-1β. Additionally, as compared to EGFR-sufficient Tg+ mice, airway epithelial cell-specific EGFR-deficient Tg+ mice exhibited significantly increased postnatal mortality, compromised bacterial clearance and elevated markers of Th2 inflammation, including Il13, Slc26a4, and Retnla. Counterintuitively, the deletion of EGFR in airway epithelial cells of Tg+ mice did not alter mucous cell metaplasia, MUC5AC/5B production, and degree of mucus obstruction. Our data shows that, unlike inflammation, muco-obstruction-relevant responses in Tg+ mice are not dependent on airway epithelial cell-specific EGFR signaling.