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

TL;DR

Exposure to low oxygen levels causes alveolar cells to age prematurely, which may contribute to a lung condition in premature infants.

Contribution

The study reveals a p53-independent p21-driven senescence pathway in alveolar cells under low hyper-oxygen exposure.

Findings

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

Autophagy inhibition leads to senolysis in cells exposed to 40% oxygen.

Alveolar epithelial cells respond differently to varying oxygen concentrations.

Abstract

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.

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