PAR2 Overexpression is Involved in the Occurrence of Hyperoxygen-Induced Bronchopulmonary Dysplasia in Rats

Abstract

Background

Bronchopulmonary dysplasia is a chronic lung disease commonly seen in preterm infants. It is characterized by delayed development of the alveoli and lung fibrosis. Protease-activated receptor 2 (PAR2) is an inflammatory driver that plays a proinflammatory role mainly through the P38 MAPK/NF-κB signaling pathway.

Methods

Newborn rat pups were kept under air or oxygen at >60% concentration. Lung tissues were collected at postnatal days (P) 1, 4, 7, and 10 to observe pathological changes and take measurements.

Results

In the hyperoxic group, P4 and P7 rats showed delayed alveolar development, septal thickening, and disturbances in alveolar structure.PAR2, P38 MAPK, NF-κB, and IL-18 expression at P4, P7, and P10 was significantly higher than in the air group.

Conclusion

PAR2 is involved in lung injury induced by persistent hyperoxia. Activated PAR2 promotes IL-18 overexpression through the P38 MAPK/NF-κB signaling pathway, which may be an important mechanism of PAR2-mediated lung injury in bronchopulmonary dysplasia.

Keywords:

• Bronchopulmonary dysplasia
• hyperoxia
• protease-activated receptor 2 (PAR2)
• P38 MAPK
• NF-κB

Acknowledgments

We would like to thank the Experimental Center of the First Affiliated Hospital of Chengdu Medical College.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Funding

This research was supported by the Sichuan Province Medical Research Project (grant number S21007), the Sichuan Province Applied Basic Research Project (grant number 2022NSFSC0787), and the Chengdu Medical Research Project (grant number 2021216).

Data availability statement

Data supporting the results or analyzed in this paper are available at https://data.mendeley.com/drafts/dkj3xnffp7