Document Type

Article

Publication Date

1-1-2022

Publication Title

Oxid Med Cell Longev

Keywords

JGM, Acute Lung Injury, Adenosine Diphosphate, Animals, Apoptosis, Caspase 3, ErbB Receptors, Humans, Hyperoxia, Lung, Lung Injury, Mice, Mice, Inbred C57BL, Oxygen, Poly(ADP-ribose) Polymerase Inhibitors

JAX Source

Oxid Med Cell Longev. 2022;2022:9518592.

Volume

2022

First Page

9518592

Last Page

9518592

ISSN

1942-0994

PMID

36193076

DOI

https://doi.org/10.1155/2022/9518592

Grant

ZMH, JJ, and BC were funded by NIH T32 training grant HL007778. ZMH is also the recipient of an NIH Loan Repay- ment Program (LRP) Award. LS is funded by the American Lung Association and Parker B Francis Fellowship. EPM is funded by a Pepper Scholar with support from the Claude D. Pepper Older Americans Independent Center at Yale School of Medicine (No. P30AG021342) and Additional Ven- tures via the Single Ventricle Research Fund. DU was funded by NIH U19 AI142733. MJK was funded by NHLBI R01HL130283 and NIA R01AG053495. JLK was funded by NIH 1R01HL125897 and NIH RFA-A1-17-040 U19.

Abstract

AIMS: Studies have linked severe hyperoxia, or prolonged exposure to very high oxygen levels, with worse clinical outcomes. This study investigated the role of epidermal growth factor receptor (EGFR) in hyperoxia-induced lung injury at very high oxygen levels (>95%).

RESULTS: Effects of severe hyperoxia (100% oxygen) were studied in mice with genetically inhibited EGFR and wild-type littermates. Despite the established role of EGFR in lung repair, EGFR inhibition led to improved survival and reduced acute lung injury, which prompted an investigation into this protective mechanism. Endothelial EGFR genetic knockout did not confer protection. EGFR inhibition led to decreased levels of cleaved caspase-3 and poly (ADP-ribosyl) polymerase (PARP) and decreased terminal dUTP nick end labeling- (TUNEL-) positive staining in alveolar epithelial cells and reduced ERK activation, which suggested reduced apoptosis

CONCLUSION: In conditions of severe hyperoxia (>95% for >24 h), EGFR inhibition led to improved survival, decreased lung injury, and reduced cell death. These findings further elucidate the complex role of EGFR in acute lung injury.

Comments

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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