Caveolin-1 modulates Notch transcriptional activity during in vitro respiratory multiciliated cell maturation

The airway epithelium, a sophisticated multicellular layer lining the respiratory tract, serves as our first line of defense against pathogens, allergens, and environmental pollutants. Recent studies have illuminated the intricate interplay between basal cell self-renewal, differentiation, and epithelial homeostasis following injury. Notably, expression of caveolin-1 (Cav-1) has been linked to specific cell types within the airway epithelium, primarily basal stem cells (BSCs) and multiciliated cells (MCCs). Despite its specific expression, the precise function of Cav-1 in BSC differentiation remains largely enigmatic. In this study, we investigate Cav-1's function within the airway epithelium in vitro, exploring the molecular mechanisms underlying BSC differentiation into MCCs and secretory cells (SCs). Our results reveal limited Cav-1 expression in mouse airway epithelial BSCs, with additional enrichment observed in MCCs. Notably, deficiency of Cav-1 accelerates MCC differentiation and maturation. Additionally, we found that Cav-1 downregulation dramatically affects Notch intracellular domain (NICD) transcriptional activity. That leads us to propose that Cav-1 participates indirectly in a transcriptional program orchestrated by NICD, thereby modulating both BSC differentiation and MCC maturation.