Activation of the endoplasmic reticulum stress pathway involving CHOP in the lungs of rats with hyperoxia‑induced bronchopulmonary dysplasia

Mol Med Rep. 2015 Sep;12(3):4494-4500. doi: 10.3892/mmr.2015.3979. Epub 2015 Jun 22.

Abstract

The molecular pathomechanisms underlying bronchopulmonary dysplasia (BPD) remain to be fully elucidated, however, lung injury is considered to be a key event. The present study was performed to determine the role of endoplasmic reticulum (ER) stress and investigate the apoptosis of alveolar epithelial cells in a BPD rat model. A total of 48 preterm Sprague‑Dawley rats were randomly divided into a control group and a hyperoxia group. The rats in the BPD group were exposed to 85% hyperoxia, while the rats in the control group were exposed to room air. A total of eight rats in each group were sacrificed 7, 14 or 21 days after exposure. The expression levels of 78‑kDa glucose‑regulated/binding immunoglobulin protein (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in the lung tissues were examined using immunohistochemistry, and the mRNA and protein levels of GRP78 and CHOP were detected using reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. In addition, the levels of apoptosis in the lung cells were evaluated suing terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling. It was demonstrated that the mRNA and protein levels of GRP78 and CHOP, and the levels of cell apoptosis in the hyperoxia group differed significantly from those in the control group (P<0.05) at different time‑points, and increased with extension of the duration of hyperoxic exposure. These data demonstrated that the ER stress pathway, involving CHOP, is activated and is important in the pathogenesis of BPD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Bronchopulmonary Dysplasia / etiology
  • Bronchopulmonary Dysplasia / metabolism*
  • Bronchopulmonary Dysplasia / pathology
  • Endoplasmic Reticulum Stress*
  • Female
  • Heat-Shock Proteins
  • Hyperoxia / complications
  • Hyperoxia / metabolism*
  • Lung / metabolism*
  • Lung / pathology
  • Male
  • Rats, Sprague-Dawley
  • Transcription Factor CHOP / metabolism*

Substances

  • Ddit3 protein, rat
  • GRP78 protein, rat
  • Heat-Shock Proteins
  • Transcription Factor CHOP