C99-07 The Role of CAVIN2+ Airway Basal Cells in COPD

Abstract Objective Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory airway disease. Airway Basal Cells (BCs) undergo specific molecular and phenotypic changes, contributing to airway remodeling following chronic inflammation. Our pre-study analysis of large - scale COPD single - cell data revealed the enrichment of CAVIN2+ BCs in COPD patients. This study aims to explore the specific mechanism of CAVIN2+ BCs in COPD, providing a new theoretical basis and intervention target for COPD treatment. Methods We integrated single - cell data of COPD lung tissues from several studies for clustering and cellular subpopulation identification. Then, we collected lung tissues and BCs from COPD patients and healthy individuals. CAVIN2+ BC subpopulations were identified by in - situ multicolor immunofluorescence. The effects of CAVIN2 on BC proliferation and differentiation were studied using cell culture and animal experiments. In vitro, we observed these effects by overexpressing or knocking down CAVIN2 using CCK8, migration, and air - liquid differentiation assays. Results Analysis of large - scale COPD single - cell data showed that CAVIN2+ BCs were enriched in COPD airways, with significantly higher gene and protein expression levels than in healthy controls. The AREG/EGFR signaling pathway plays a key role in the interaction between macrophages and CAVIN2+ BCs, influencing airway remodeling in COPD. In situ multicolor immunohistochemistry of lung tissues from COPD and control subjects confirmed the increased proportion of CAVIN2+ BCs in COPD airways. In vitro experiments revealed that CAVIN2 knockdown promoted airway basal stem cell proliferation and migration, while overexpression inhibited these processes. Air - liquid differentiation in vitro showed that CAVIN2 overexpression increased the proportion of cells differentiating into mucus - secreting cells (expressing MUC5AC), while CAVIN2 knockdown increased ciliated cell differentiation (expressing Ac - Tub). Conclusion CAVIN2+ BCs play a key role in airway remodeling in COPD. This study offers new insights into COPD pathological mechanisms and provides a theoretical basis for future COPD therapeutic strategies based on stem cell modulation. This abstract is funded by: None