Document Type
Article
Publication Date
1-27-2026
Original Citation
Harris Z,
Korde A,
Khoury J,
Manning E,
Stanley G,
Shin Y,
Mitchell K,
von der Schulenburg A,
Sun Y,
Hu B,
Shin H,
Joerns J,
Clark B,
Placek L,
Unutmaz D,
Moldobaeva A,
Sharma L,
Sauler M,
Rajagopalan G,
Zhang X,
Wang H,
Ghaedi M,
Kang M,
Koff J.
Epidermal growth factor receptor regulates Beclin-1 in hyperoxic acute lung injury. BMJ Open Respir Res. 2026;13(1):e003323.
Keywords
JMG, Animals, Acute Lung Injury, Beclin-1, ErbB Receptors, Mice, Autophagy, Hyperoxia, Disease Models, Animal, Humans, Male, Lung, Mice, Inbred C57BL
JAX Source
BMJ Open Respir Res. 2026;13(1):e003323.
ISSN
2052-4439
PMID
41592865
DOI
https://doi.org/10.1136/bmjresp-2025-003323
Abstract
BACKGROUND: While delivery of supplemental oxygen is a life-saving therapy, exposure to high oxygen, called hyperoxia, leads to increased intensive care unit mortality. Hyperoxia induces oxidant-mediated acute lung injury (ALI) and pulmonary cell death, called hyperoxic ALI (HALI). Elucidating molecular mechanisms in HALI could identify therapeutic targets in ALI.
METHODS: In the current study, we examined in vivo effects of HALI on Beclin-1 (BCN1), which regulates autophagy, and modulation of BCN1 by epidermal growth factor receptor (EGFR). Effects of HALI on BCN1 and autophagy were examined in mice with genetically decreased EGFR (EGFR
RESULTS: In WT, HALI led to increased BCN1 (59% increased total BCN1/β-Actin; p< 0.01) in lung and alveolar epithelium (484% increased H-score; p< 0.001). HALI led to decreased microtubule-associated protein 1B-light chain (LC3B)-II/-I ratios (43% decrease; p< 0.05) and increased p62 (93% increase; p< 0.05), suggesting reduced autophagic flux. In human alveolar type-II cells derived from induced pluripotent stem cells (AT2s
CONCLUSIONS: These data delineate a novel cell death pathway in HALI involving BCN1 and EGFR with therapeutic potential.
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