Open Access

Effect of the Notch4/Dll4 signaling pathway in early gestational intrauterine infection on lung development

  • Authors:
    • Canyang Zhan
    • Yi Sun
    • Jiarong Pan
    • Lihua Chen
    • Tianming Yuan
  • View Affiliations

  • Published online on: July 8, 2021     https://doi.org/10.3892/etm.2021.10404
  • Article Number: 972
  • Copyright: © Zhan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intrauterine infection is an important risk factor for bronchopulmonary dysplasia (BPD). BPD is characterized by arrested lung alveolarization and impaired pulmonary vascularization. The Notch4 signaling pathway is a key regulator of vascular remodeling and angiogenesis. Therefore, the presents study investigated the expression of Notch4, delta‑like canonical Notch ligand 4 (Dll4) and related factors in an in vivo rat model and in rat pulmonary microvascular endothelial cells (PMVECs) in vitro, to study the mechanisms by which intrauterine infection affects rat lung development. A rat model of intrauterine infection was established by endocervical inoculation with Escherichia scoli on embryonic day 15. The date of birth was counted as postnatal day 0 (P0). Then, the lung tissues were collected from pups at days P3‑P14. The expression of Notch4, Dll4 and related factors was measured by reverse transcription‑quantitative PCR and western blotting. In addition, the γ‑secretase inhibitor DAPT was used to examine the effect of Notch4 signaling on PMVECs. Intrauterine E. coli infection impaired normal lung development, as indicated by decreased microvessel density, fewer alveoli, fewer secondary septa, and larger alveoli compared with the control group. Furthermore, Notch4, Dll4 and NF‑κB levels were significantly increased in the E. coli‑infected group at P3 compared with the control group. Similarly, the mRNA expression levels of fetal liver kinase 1 (Flk‑1, a VEGF receptor) were significantly increased in the E. coli‑infected group at P3 and P7. In PMVECs, the inhibition of Notch4 signaling contributed to decreases in lipopolysaccharide (LPS)‑induced expression of VEGF and its receptors. Furthermore, the inhibition of Notch4/Dll4 signaling accelerated cell proliferation and decreased the apoptosis rate of LPS‑induced PMVECs. LPS‑induced NF‑κB expression in PMVECs was also attenuated by the Notch4/Dll4 inhibitor. In conclusion, intrauterine E. coli infection impaired normal lung development, possibly through Notch4/Dll4 signaling and effects on VEGF and its receptors.
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September-2021
Volume 22 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhan C, Sun Y, Pan J, Chen L and Yuan T: Effect of the Notch4/Dll4 signaling pathway in early gestational intrauterine infection on lung development. Exp Ther Med 22: 972, 2021
APA
Zhan, C., Sun, Y., Pan, J., Chen, L., & Yuan, T. (2021). Effect of the Notch4/Dll4 signaling pathway in early gestational intrauterine infection on lung development. Experimental and Therapeutic Medicine, 22, 972. https://doi.org/10.3892/etm.2021.10404
MLA
Zhan, C., Sun, Y., Pan, J., Chen, L., Yuan, T."Effect of the Notch4/Dll4 signaling pathway in early gestational intrauterine infection on lung development". Experimental and Therapeutic Medicine 22.3 (2021): 972.
Chicago
Zhan, C., Sun, Y., Pan, J., Chen, L., Yuan, T."Effect of the Notch4/Dll4 signaling pathway in early gestational intrauterine infection on lung development". Experimental and Therapeutic Medicine 22, no. 3 (2021): 972. https://doi.org/10.3892/etm.2021.10404