Low hyper-oxygen exposure induces p21-dependent p53-independent senescence in alveolar cells.

Bronchopulmonary dysplasia (BPD) is a chronic pulmonary condition predominantly affecting premature neonates who necessitate oxygen therapy. Currently, BPD is classified into two types-old and new BPD-that differ in histology and pathology. The new BPD is observed in premature infants exposed to gentle ventilation and low oxygen concentrations, emphasizing the disruption of normal development. This study assessed the effects of low-to-high oxygen concentrations on rat alveolar epithelial L2 cells, aiming to mimic clinical scenarios. Exposure to 40 % oxygen induced p53-independent p21 expression in alveolar cells, resulting in G1-cell cycle exit cellular senescence. The inhibition of autophagy induced senolysis in L2 cells exposed to 40 % oxygen. Alveolar epithelial cells exhibit distinct responses to varying oxygen concentrations. Elucidating the interaction between senescence and autophagy is crucial for understanding the pathogenesis of novel bronchopulmonary dysplasia (BPD) in premature infants, thereby identifying potential preventive strategies.