Fig 1. Endoplasmic reticulum (ER) stress is increased in bronchopulmonary dysplasia (BPD).

(A) Representative images of human lungs from non-BPD and BPD infants. The BPD lungs have a simplified alveolar structure, thickened alveolar walls, denuded epithelial cells, and inflammatory cell infiltration. The increased co-localization of phospho-IRE1α (green) and type 1 alveolar epithelial cells (AT1, red) indicates increased ER stress in human BPD lungs. The integrated fluorescent density of colocalized (white arrows) phospho-IRE1α fluorescence and AT1 is significantly increased in BPD lungs (2.7x10⁶–1.7x10⁷ vs. 1.2x10⁶–1.2x10⁷, n = 10, p = 0.0012 by Wilcoxon signed-rank test) than the age- and gender-matched (6 males and 4 females) control non-BPD lungs. (B) Phospho-PERK (green) and AT1 (red) were used to detect ER stress in rat lungs. The colocalization (white arrows) is markedly increased in HOX (hyperoxia, >90% O₂) BPD rat lungs at postnatal day 10 (P10). (C) The transcriptomic study is done by Affymetrix GeneChip™ Rat Genome 230 2.0 Array (n = 6 for both NOX and HOX; 3 males and 3 females in each group) on RNA obtained from lungs at P10. Gene expressions reaching significant differences (p<0.05) with FDR <0.1 are selected and uploaded into ToppGene for gene enrichment analysis and annotation per Gene Ontology Biological Processes. Totally 118 genes involved in response to ER stress (GO:0034976) are significantly upregulated in hyperoxic rat lungs, as shown in the heatmap. Markers commonly used to demonstrate an increased ER stress are highlighted in red squares. *: p<0.05.