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Vitamin E relieves chronic obstructive pulmonary disease by inhibiting COX2-mediated p-STAT3 nuclear translocation through the EGFR/MAPK signaling pathway

Abstract

Patients with chronic obstructive pulmonary disease (COPD) are characterized by an imbalance between oxidant enzymes and antioxidant enzymes. In the present study, we explored the protective effect of vitamin E on COPD and the underlying mechanisms. Targets of vitamin E were predicted by bioinformatics analysis. After establishing cigarette smoke (CS)-induced COPD rats, the expression levels of epidermal growth factor receptor (EGFR), cyclooxygenase 2 (COX2), and transcriptional activity of signal transducer and activator of transcription 3 (STAT3) were measured. Additionally, the effects of vitamin E on CS-induced COPD were explored by assessing inflammation, the reactive oxygen species (ROS), the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA), viability of human bronchial epithelioid (HBE) cells, and the expression of EGFR/MAPK pathway-related factors after loss- and gain- function assays. Vitamin E alleviated COPD. Vitamin E inhibited MAPK signaling pathway through decreasing EGFR expression. Additionally, vitamin E suppressed CS-induced HBE cell damage. Functionally, vitamin E attenuated CS-induced inflammation, apoptosis, and ROS by inhibiting the EGFR/MAPK axis, thereby inhibiting COX2-mediated p-STAT3 nuclear translocation. Moreover, overexpression of COX2 attenuated the protective effect of vitamin E on COPD rats. The present study shows that vitamin E inhibits the expression of COX2 by negatively regulating the EGFR/MAPK pathway, thereby inhibiting the translocation of phosphorylated STAT3 to the nucleus and relieving COPD.

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Fig. 1: Vitamin E attenuates apoptosis, inflammation, and ROS production in the lungs of COPD rats.
Fig. 2: Vitamin E downregulates EGFR and inactivates MAPK signaling pathway.
Fig. 3: Vitamin E relieves CS-induced HBE cell damage.
Fig. 4: Vitamin E negatively regulates the EGFR/MAPK pathway to inhibit COX2-mediated STAT3 nuclear entry.
Fig. 5: Vitamin E inhibits apoptosis, inflammation, and ROS production in the lungs of COPD rats through EGFR/MAPK1/COX2/STAT3 axis.
Fig. 6: The mechanism graph of the regulatory function of Vitamin E in COPD.

Data availability

The datasets generated/analyzed during the current study are available.

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Acknowledgements

We would like to give our sincere appreciation to the reviewers for their helpful comments on this article.

Author contributions

HZ, JG, LL, SZ, GY, PL, RL, and JL designed the study. LL, SZ, GY, PL, RL, and JL collated the data, carried out data analyses, and produced the initial draft of the paper. HZ, JG contributed to drafting the paper. All authors have read and approved the final submitted paper.

Funding

This work is supported by Special Fund Project for the Central Government to Guide Local Science and Technology Development (YDZX20191400004736); Shanxi Province Key R&D Program (International Science and Technology Cooperation) Project (201903D421058).

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Correspondence to Hui Zhao.

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All animal experiments were approved by the Animal Care and Use Committee of The Second Hospital of Shanxi Medical University and in accordance with the guidance of National Institutes of Health. Great efforts were made to minimize the number of animals used in the experiments and their suffering.

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The authors declare no competing interests.

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Zhao, H., Gong, J., Li, L. et al. Vitamin E relieves chronic obstructive pulmonary disease by inhibiting COX2-mediated p-STAT3 nuclear translocation through the EGFR/MAPK signaling pathway. Lab Invest (2021). https://doi.org/10.1038/s41374-021-00652-z

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