Correlation Between CAV-1 and PTEN-Mediated Apoptosis in Hyperoxia-Induced Acute Lung Injury

Respiratory support is essential in the clinical management of critically ill patients; however, prolonged exposure to high concentrations of oxygen can result in hyperoxia-induced acute lung injury (HALI). In this study, we developed a model of hyperoxia exposure utilizing C57BL/6 mice and human bronchial epithelial (BEAS-2B) cells. We employed CAV-1 siRNA transfection and CAV-1 expression plasmid techniques to analyze the effects of hyperoxia on the expression of caveolin-1 (CAV-1), the deletion of the phosphatase and tensin homolog (PTEN) gene on chromosome 10, and the apoptotic markers Bax and Bcl-2. Additionally, we explored the mechanisms by which CAV-1 regulates PTEN-mediated apoptosis in the context of HALI. Our findings aim to provide valuable insights for developing effective preventive and therapeutic strategies to combat this condition.

First, we established a hyperoxia-induced acute lung injury (HALI) model in male C57BL/6 mice. Histopathological examination was conducted using hematoxylin-eosin staining to evaluate the pathological changes and the severity of lung tissue damage. Next, we developed an in vitro HALI model utilizing the BEAS-2B cell line. Subsequently, CAV-1 siRNA and CAV-1 expression plasmids were transfected into BEAS-2B cells. We quantified the expression levels of CAV-1, PTEN, Bax, and Bcl-2 using reverse transcription polymerase chain reaction (RT-PCR) and immunoblotting techniques. Additionally, the impact of altered CAV-1 expression on apoptosis in BEAS-2B cells was assessed through flow cytometry.

Exposure to hyperoxia led to pathological alterations in mice's lung tissue, increased the CAV-1, PTEN, and Bax expression levels, and decreased Bcl-2 expression. Initially, there were no notable variances in the expression levels of CAV-1, PTEN, and Bax in the cells. However, as the exposure time to hyperoxia prolonged, there was a significant increase in both mRNA and protein expression levels of CAV-1 and PTEN, while Bcl-2 exhibited a significant decrease. Moreover, CAV-1 knockdown attenuated the expression of PTEN and Bax, and elevated the expression of Bcl-2. However, CAV-1 overexpression showed an opposite result. The expression levels of CAV-1, PTEN, and Bax were positively correlated in mice and cell models, and negatively correlated with those of Bcl-2. Additionally, downregulation of CAV-1 suppressed apoptosis in BEAS-2B cells.

Our results indicate that CAV-1 plays a pivotal role in regulating the expression of PTEN and the apoptosis-related factors Bax and Bcl-2 in a hyperoxic environment. This regulatory function of CAV-1 on PTEN and its downstream apoptotic pathways suggests a significant correlation between CAV-1 and PTEN-mediated apoptosis. Consequently, CAV-1 is involved in the development of hyperoxic lung injury (HALI) through the PTEN-mediated apoptotic pathway. These findings offer new insights into the molecular mechanisms underlying the pathogenesis of HALI and underscore the potential therapeutic implications of targeting CAV-1 in the management of this condition.