Muco-Obstructive Lung Disease Exhibits Distinct Hypoxic and Inflammatory Airway Epithelial Gene Pathways

ABSTRACT: Intraluminal obstruction produces chronic airway epithelial hypoxia. We investigated how chronic airway epithelial hypoxia and inflammatory stimuli (supernatatants of mucopurulent materials: SMM) interact in human bronchial epithelial (HBE) cultures and resected bronchiectatic lungs to produce the diseased epithelial environment characteristic of muco-obstructive diseases. Results: Hypoxia and supernatants of mucopurulent materials (SMM) regulated largely separate transcriptional programmes regardless of treatment order. PTGS2 and CXCL8 represented a small number of genes additively upregulated by both hypoxia and SMM. HIF1A knockdown and EPAS1 knockdown produced distinct, often opposing, effects on hypoxia-responsive pathways. HIF1A dominated upregulation of glycolytic pathway signalling. EPAS1 regulated genes that increase mucus concentration under hypoxia (e.g., SCNN1G). Conclusion: Chronic hypoxia and inflammation regulated distinct genes/pathways that combine to produce complex diseased environments in muco-obstructed airways. HIF1α and EPAS1 regulated distinct hypoxia-induced transcriptional responses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE314018 | GEO | 2026/06/15

REPOSITORIES: GEO