Nrf2‑Keap1‑ARE‑NQO1 signaling attenuates hyperoxia‑induced lung cell injury by inhibiting apoptosis

Weng,Bowen; Zhang,Xiaoyue; Chu,Xiaoyun; Gong,Xiaohui; Cai,Cheng

doi:10.3892/mmr.2021.11860

Nrf2‑Keap1‑ARE‑NQO1 signaling attenuates hyperoxia‑induced lung cell injury by inhibiting apoptosis

Authors:
- Bowen Weng
- Xiaoyue Zhang
- Xiaoyun Chu
- Xiaohui Gong
- Cheng Cai
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Affiliations: Department of Neonatology, Children's Hospital Affiliated to Shanghai Jiaotong University, Shanghai Children's Hospital, Shanghai 200062, P.R. China
Published online on: January 21, 2021 https://doi.org/10.3892/mmr.2021.11860
Article Number: 221

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Abstract

Bronchopulmonary dysplasia (BPD) is one of the main causes of chronic lung disease in premature infants. Acute lung injury following exposure to hyperoxia contributes to the development of BPD in preterm infants. The nuclear factor‑erythroid 2‑related factor 2 (Nrf2) signaling pathway is an endogenous antioxidant defense mechanism that is involved in the pathogenesis of numerous hyperoxia‑induced diseases. In the present study, the expression of Nrf2, Kelch‑like ECH‑associated protein 1 (Keap1) and NAD(P)H quinone oxidoreductase 1 enzyme (NQO1) was detected in A549 cells exposed to hyperoxia and transfection with small interfering RNA (siRNA) using reverse transcription‑quantitative polymerase chain reaction and western blotting, and cellular apoptosis was detected using flow cytometry. The results demonstrated that apoptosis increased significantly following exposure of the cells to hyperoxia, and Nrf2, Keap1 and NQO1 expression levels were significantly upregulated under hyperoxic conditions. Furthermore, following transfection with Nrf2 siRNA, the expression levels of these genes were significantly downregulated and apoptosis was significantly increased compared with the respective values in untransfected cells. These findings suggest that the Nrf2‑Keap1‑antioxidant response element‑NQO1 signaling pathway may play a protective role in hyperoxia‑induced lung injury via the inhibition of apoptosis.

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