Airway epithelial cells promote in vitro airway smooth muscle cell proliferation by activating the Wnt/β-catenin pathway

Asthma is a common chronic inflammatory airway disease, imposing a substantial health and economic burden on society and individuals. Current treatments primarily focus on symptom relief and lung function improvement, often failing to address the underlying pathology. Thus, exploring new therapeutic approaches is crucial. Airway smooth muscle cells (ASMCs) play a key role in regulating airway tone and airflow, while abnormal ASMCs proliferation contributes to airway remodeling in asthma. Airway epithelial cells (AECs), serving as the first barrier against pathogens and allergens, also have critical immune functions.

This study focuses on the interaction between AECs and ASMCs, as AECs are more accessible for drug delivery due to their location at the airway surface. Investigating this relationship could facilitate novel interventions targeting AECs to inhibit pathological ASMCs activity. In our experiment, we isolated ASMCs and AECs from healthy mice and found that AECs significantly promoted ASMCs proliferation in co-culture. RNA sequencing revealed that this process might be linked to the activation of the canonical Wnt signaling pathway in ASMCs. By using Wnt pathway inhibitors (endo-IWR1) and siRNA to disrupt Wnt receptors, we reversed this phenotype. This finding suggests that AECs may promote ASMCs proliferation by activating the Wnt pathway in ASMCs. The Wnt/β-catenin pathway appears to play an important role in ASMCs proliferation, indicating that future pathological studies should consider the potential involvement of the Wnt pathway in airway remodeling.