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Effects of PGE1 on the ERS pathway in neonatal rats with hyperoxic lung injury

Pediatric Research volume 97, pages 835–842 (2025)Cite this article

Abstract

Background

With the increase in the number of low birth weight infants, oxygen therapy is more widely used. However, chronic high-concentration oxygen environments lead to hyperoxic lung injury in children, which in turn leads to bronchopulmonary dysplasia (BPD). PGE1 is widely used in the clinic for its ability to inhibit inflammation and improve circulation. Therefore, we further investigated whether PGE-1 has a therapeutic effect on hyperoxic lung injury.

Methods

Hyperoxic lung injury model was adopted for investigating the interventional effects and underlying mechanisms of intraperitoneal injection of prostaglandin E1 (PGE-1) on hyperoxic lung injury in newborn rats via relevant experimental techniques, such as Diff-Quick staining, lung wet dry specific gravity measurements, HE staining, TUNEL staining, ELISA, and the Western blot method.

Results

Inflammatory and apoptotic cells in the PGE1-treated group were significantly lower than those in the hyperoxic lung injury group (p < 0.05); and the contents of IL-1β, IL-6 and TNF-α in the treated group were significantly lower than those in the model group (p < 0.05). Caspase-3, CHOP, GRP78 and Bcl-2/Bax protein expression in the treatment group was significantly lower than that in the model group (p < 0.05).

Conclusion

PGE-1 has a therapeutic effect on hyperoxic lung injury in neonatal rats.

Impact

  • PGE1 treatment reduces levels of inflammatory cells and pro-inflammatory cytokines and decreases apoptosis.

  • PGE1 has a therapeutic effect on BPD through the endoplasmic reticulum stress pathway.

  • This study offers the possibility of PGE1 for the treatment of BPD.

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Fig. 1: Changes in the body weight of neonatal rats in each group (n = 10).
Fig. 2: Determination of the W/D ratio in the lung tissue of each group (n = 10).
Fig. 3
Fig. 4
Fig. 5: Contents of leukocytes in the BALF of neonatal rats from diverse groups (n = 10).
Fig. 6
Fig. 7: Apoptosis indices of neonatal rat lung tissues from the different groups (n = 10, \(\bar{{{{{{\rm{X}}}}}}}\pm {{{{{\rm{S}}}}}}\)).
Fig. 8: IL-1β levels in lung tissues from neonatal rats in each group at different time points (n = 10,\(\bar{x}\pm s\)).
Fig. 9: IL-6 levels in lung tissues from neonatal rats in each group at varying time points (n = 10).
Fig. 10: TNF-α levels in lung tissues from neonatal rats in each group at varying time points (n = 10).
Fig. 11
Fig. 12: Changes in CHOP protein levels in lung tissues from different periods in each group.
Fig. 13: Changes in GRP78 protein levels in lung tissues from each group at different time points.
Fig. 14: Changes in caspase-3 protein expression in lung tissues from different groups at different time points.
Fig. 15: Changes in the Bcl2/Bax ratio in lung tissues from different groups at different time points.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Geng, N. et al. Prostaglandin E1 administration for prevention of contrast-induced acute kidney injury: a systematic review and meta-analysis of randomized controlled trials. Medicine 97, e11416 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wang, S. & Kaufman, R. J. The impact of the unfolded protein response on human disease. J. Cell Biol. 197, 857–867 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Tamaki, T. et al. A novel transmembrane protein defines the endoplasmic reticulum stress-induced cell death pathway. Biochem. Biophys. Res. Commun. 486, 149–155 (2017).

    Article  CAS  PubMed  Google Scholar 

  4. Rozpedek, W. et al. The role of the PERK/eIF2α/ATF4/CHOP signaling pathway in tumor progression during endoplasmic reticulum stress. Curr. Mol. Med. 16, 533–544 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Fernandes-Alnemri, T., Litwack, G. & Alnemri, E. S. CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. J. Biol. Chem. 269, 30761–30764 (1994).

    Article  CAS  PubMed  Google Scholar 

  6. Rao, R. V. et al. Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78. FEBS Lett. 514, 122–128 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yuan, J., Shaham, S., Ledoux, S., Ellis, H. M. & Horvitz, H. R. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75, 641–652 (1993).

    Article  CAS  PubMed  Google Scholar 

  8. Schrör, K. & Hohlfeld, T. Mechanisms of anti-ischemic action of prostaglandin E1 in peripheral arterial occlusive disease. Vasa 33, 119–124 (2004).

    Article  PubMed  Google Scholar 

  9. Liu, B. et al. Lipo‑prostaglandin E1 modifies cognitive impairment in rats with vascular cognitive impairment by promoting angiogenesis via the VEGF/VEGFR pathway. Mol. Med. Rep. 16, 3117–3124 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hafez, T. et al. The effect of intraportal prostaglandin E1 on adhesion molecule expression, inflammatory modulator function, and histology in canine hepatic ischemia/reperfusion injury. J. Surg. Res. 138, 88–99 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Warner, B. B., Stuart, L. A., Papes, R. A. & Wispé, J. R. Functional and pathological effects of prolonged hyperoxia in neonatal mice. Am. J. Physiol. 275, L110–L117 (1998).

    CAS  PubMed  Google Scholar 

  12. Fiebich, B. L. et al. Prostaglandin E2 induces interleukin-6 synthesis in human astrocytoma cells. J. Neurochem. 68, 704–709 (1997).

    Article  CAS  PubMed  Google Scholar 

  13. Yang, M., Chen, Y., Huang, X., Shen, F. & Meng, Y. ETS1 ameliorates hyperoxia-induced bronchopulmonary dysplasia in mice by activating Nrf2/HO-1 mediated ferroptosis. Lung 201, 425–441 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Xu, C., Xue, D. & Jin, Z. Effects of insulin-like growth factor 1 on hyperoxic lung injury in neonatal rats and its mechanism discussion. Shandong Med 56, 37–39 (2016).

    Google Scholar 

  15. Ozdemir, R. et al. Colchicine protects against hyperoxic lung injury in neonatal rats. Neonatology 102, 265–269 (2012).

    Article  CAS  PubMed  Google Scholar 

  16. Jia, D. et al. Ferroptosis is involved in hyperoxic lung injury in neonatal rats. J. Inflamm. Res. 14, 5393–5401 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pritchard, K. A. Jr et al. Role of endoplasmic reticulum stress in impaired neonatal lung growth and bronchopulmonary dysplasia. PLoS ONE 17, e0269564 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ron, D. & Walter, P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 8, 519–529 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Jin, R. et al. The interaction of S100A16 and GRP78 actives endoplasmic reticulum stress-mediated through the IRE1α/XBP1 pathway in renal tubulointerstitial fibrosis. Cell Death Dis. 12, 942 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Oyadomari, S. & Mori, M. Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 11, 381–389 (2004).

    Article  CAS  PubMed  Google Scholar 

  21. Lu, M. et al. Opposing unfolded-protein-response signals converge on death receptor 5 to control apoptosis. Science 345, 98–101 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Shakeri, R., Kheirollahi, A. & Davoodi, J. Apaf-1: regulation and function in cell death. Biochimie 135, 111–125 (2017).

    Article  CAS  PubMed  Google Scholar 

  23. Sun, D. K., Wang, L. & Zhang, P. Antitumor effects of chrysanthemin in PC-3 human prostate cancer cells are mediated via apoptosis induction, caspase signalling pathway and loss of mitochondrial membrane potential. Afr. J. Tradit. Complement. Altern. Med. 14, 54–61 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ahmed, F. F., Abd El-Hafeez, A. A., Abbas, S. H., Abdelhamid, D. & Abdel-Aziz, M. New 1,2,4-triazole-chalcone hybrids induce caspase-3 dependent apoptosis in A549 human lung adenocarcinoma cells. Eur. J. Med. Chem. 151, 705–722 (2018).

    Article  CAS  PubMed  Google Scholar 

  25. Rogers, C. et al. Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation. Nat. Commun. 10, 1689 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Pediatrics, Yanbian University Hospital, Yanji, 133000, China

    Zhenlin Yang, Jingjing Guo, Jiarui Li, Fan Gao, Weiwei Zheng, Zhengyong Jin & Jinzi Li

  2. Liaocheng City Hospital of Traditional Chinese, Liaocheng, 252000, China

    Jianing Song

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  1. Zhenlin Yang
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Contributions

Zhenlin Yang contributed to the performed the experiments and wrote the original draft of the manuscript. Zhengyong Jin and Jinzi Li performed the relevant literature research and revised the manuscript. Jianing Song and Fan Gao contributed to the literature search and processing of the findings. Jingjing Guo, Jiarui Li and Weiwei Zheng contributed reagents, materials, and analysis tools; all authors read and approved the final manuscript for publication.

Corresponding author

Correspondence to Jinzi Li.

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The authors declare no competing interests.

Ethical approval

All animal experiments were carried out according to the ethical policies and the procedures approved by the Institutional Animal Use and Care Committee of Yanbian University of Science and Technology.

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Yang, Z., Song, J., Guo, J. et al. Effects of PGE1 on the ERS pathway in neonatal rats with hyperoxic lung injury. Pediatr Res 97, 835–842 (2025). https://doi.org/10.1038/s41390-024-03381-3

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