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Am J Perinatol 2024; 41(S 01): e2365-e2375
DOI: 10.1055/s-0043-1771258
Original Article

Protective Effect and Mechanism of Autophagy in Endothelial Cell Injury Induced by Hyperoxia

Xiaodan Zhu  
1   Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China
2   Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
3   Sichuan Clinical Research Center for Birth Defects, Luzhou, China
,
Shasha He   
1   Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China
2   Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
3   Sichuan Clinical Research Center for Birth Defects, Luzhou, China
,
Rong Zhang
1   Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China
2   Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
3   Sichuan Clinical Research Center for Birth Defects, Luzhou, China
,
Lan Kang
1   Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China
2   Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
3   Sichuan Clinical Research Center for Birth Defects, Luzhou, China
,
Xiaoping Lei
1   Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China
2   Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
3   Sichuan Clinical Research Center for Birth Defects, Luzhou, China
,
Wenbin Dong
1   Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China
2   Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
3   Sichuan Clinical Research Center for Birth Defects, Luzhou, China
› Author Affiliations Funding This study was supported by the National Natural Science Foundation of China (81571480), major science and technology projects of Sichuan Science and Technology Department (22DYF1470), the Luzhou-Southwest Medical University Science and Technology Strategic Cooperation Project (2020LZXNYDJ03) and the Southwest Medical University scientific research project (2021KQN069).
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Abstract

Objective Bronchopulmonary dysplasia is a chronic lung disease in premature infants with alveolar simplification and pulmonary vascular development disorder as the main pathological feature and hyperoxia as the main etiology. Autophagy is a highly conserved cytological behavior of self-degrading cellular components and is accompanied by oxidative stress. Studies have reported that autophagy is regulated by FOXO1 posttranslational modification. However, whether autophagy can be involved in the regulation of endothelial cell injury induced by hyperoxia and its mechanism are still unclear.

Study Design We have activated and inhibited autophagy in human umbilical vein endothelial cells under hyperoxia and verified the role of autophagy in endothelial cell-related functions from both positive and negative aspects.

Results Our research showed that the expression level of autophagy-related proteins decreased, accompanied by decreased cell migration ability and tube formation ability and increased cell reactive oxygen species level and cell permeability under hyperoxia conditions. Using an autophagy agonist alleviated hyperoxia-induced changes and played a protective role. However, inhibition of autophagy aggravated the cell damage induced by hyperoxia. Moreover, the decrease in autophagy proteins was accompanied by the upregulation of FOXO1 phosphorylation and acetylation.

Conclusion We concluded that autophagy was a protective mechanism against endothelial cell injury caused by hyperoxia. Autophagy might participate in this process by coregulating posttranslational modifications of FOXO1.

Key Points

  • Hyperoxia induces vascular endothelial cell injury.

  • Autophagy may has a protective role under hyperoxia conditions.

  • FOXO1 posttranslational modification may be involved in the regulation of autophagy.

Keywords

bronchopulmonary dysplasia - autophagy - FOXO1 - rapamycin - 3-methyladenine

Authors' Contributions

X.Z. mainly designed the research, analyzed the data, and prepared the figures. S.H. mainly performed the experiments and drafted the manuscript. X.Z., S.H., R.Z., L.K., X.L., and W.D. participated in the design of the research and approved the final version of the manuscript.


Conflict of Interest

None declared.


# These authors contributed equally to this work.




Publication History

Received: 01 February 2023

Accepted: 19 June 2023

Article published online:
29 July 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
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