B109-24 Serpinb3 Mediates Cigarette Smoke-induced Panoptosis and Mucus Hypersecretion in Bronchial Epithelium

Background

Chronic Obstructive Pulmonary Disease (COPD) is a smoking-associated chronic airway disease characterized by persistent airflow reduction. The airway epithelium, which serves as the first line of defense against the environment, plays a central role in the initiation and progression of chronic airway diseases. Airway epithelium in COPD patients is characterized by hyperplasia of mucus-producing goblet cells and a reduction in ciliated cells; however, the key epithelial molecules underlying these pathological changes remain under investigation.

Methods

We performed single-cell RNA sequence of end-stage COPD lung tissues and further bioinformatic analysis. To further investigate the role of COPD related basal cells, we employed standard molecular techniques in primary basal cells for precise mechanistic validation.

Results

Single-cell RNA sequence analysis reveals a specific basal cell cluster in COPD, which showed significantly higher expression of SERPINB3. Bioinformatic analysis and molecular techniques showed that COPD related basal cells exhibit enhanced panoptosis and mucus hypersecretion through SERPINB3. Targeting SERPINB3 or the panoptosis pathway attenuates inflammatory responses and mucus hypersecretion in COPD.

Conclusion

SERPINB3 promotes mucus hypersecretion and inflammation in COPD airways by inducing panoptosis in airway basal cells. SERPINB3 plays a key role in governing COPD susceptibility and disease progression.

This abstract is funded by: None