Hyperoxia induces endoplasmic reticulum stress‑associated apoptosis via the IRE1&alpha; pathway in rats with bronchopulmonary dysplasia

Tong,Xin; Li,Mengyun; Liu,Na; Huang,Wanjie; Xue,Xindong; Fu,Jianhua

doi:10.3892/mmr.2020.11671

Hyperoxia induces endoplasmic reticulum stress‑associated apoptosis via the IRE1α pathway in rats with bronchopulmonary dysplasia

Authors:
- Xin Tong
- Mengyun Li
- Na Liu
- Wanjie Huang
- Xindong Xue
- Jianhua Fu
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Affiliations: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: November 9, 2020 https://doi.org/10.3892/mmr.2020.11671
Article Number: 33
Copyright: © Tong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in premature infants, and alveolar dysplasia and pulmonary vascular development disorders are the predominant pathological features. Apoptosis of lung epithelial cells is a key factor in the pathological process of alveolar developmental arrest. Endoplasmic reticulum stress (ERS)‑associated apoptosis is a noncanonical apoptotic pathway involved in the development of several pulmonary diseases. Previous studies have demonstrated that protein kinase RNA‑like endoplasmic reticulum kinase, inositol‑requiring enzyme 1α (IRE1α) and activating transcription factor 6 can initiate the apoptosis signaling pathway mediated by ERS and induce apoptosis of injured cells. Among them, the IRE1α pathway is the most conservative pathway in the unfolded protein response, which serves an important role in a number of pathological environments, to the extent of determining cell fate; however, it is rarely reported in BPD. Based on the establishment of a rat BPD model, the present study verified the activation of ERS in BPD and further confirmed that prolonged ERS inhibited the protective pathway, IRE1α/X‑box binding proteins, and activated the proapoptotic pathway, IRE1α/c‑Jun N‑terminal kinase, to induce the apoptosis of lung epitheliums.

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