Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
September-2021 Volume 22 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2021 Volume 22 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article 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 / Copyright

    Affiliations: Department of Neonatology, Children's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
    Copyright: © Zhan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 972
    |
    Published online on: July 8, 2021
       https://doi.org/10.3892/etm.2021.10404
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



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.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Zysman-Colman Z, Tremblay GM, Bandeali S and Landry JS: Bronchopulmonary dysplasia-trends over three decades. Paediatr Child Health. 18:86–90. 2013.PubMed/NCBI View Article : Google Scholar

2 

Jobe AH: What is BPD in 2012 and what will BPD become? Early Hum Dev. 88:S27–S28. 2012.PubMed/NCBI View Article : Google Scholar

3 

Thébaud B and Abman SH: Bronchopulmonary dysplasia: Where have all the vessels gone? Roles of angiogenic growth factors in chronic lung disease. Am J Respir Crit Care Med. 175:978–985. 2007.PubMed/NCBI View Article : Google Scholar

4 

De Paepe ME, Greco D and Mao Q: Angiogenesis-related gene expression profiling in ventilated preterm human lungs. Exp Lung Res. 36:399–410. 2010.PubMed/NCBI View Article : Google Scholar

5 

Stenmark KR and Abman SH: Lung vascular development: Implications for the pathogenesis of bronchopulmonary dysplasia. Annu Rev Physiol. 67:623–661. 2005.PubMed/NCBI View Article : Google Scholar

6 

Hartling L, Liang Y and Lacaze-Masmonteil T: Chorioamnionitis as a risk factor for bronchopulmonary dysplasia: A systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 97:F8–F17. 2012.PubMed/NCBI View Article : Google Scholar

7 

Cao L, Wang J, Tseu I, Luo D and Post M: Maternal exposure to endotoxin delays alveolarization during postnatal rat lung development. Am J Physiol Lung Cell Mol Physiol. 296:L726–L737. 2009.PubMed/NCBI View Article : Google Scholar

8 

Kim DH, Choi CW, Kim EK, Kim HS, Kim BI, Choi JH, Lee MJ and Yang EG: Association of increased pulmonary interleukin-6 with the priming effect of intra-amniotic lipopolysaccharide on hyperoxic lung injury in a rat model of bronchopulmonary dysplasia. Neonatology. 98:23–32. 2010.PubMed/NCBI View Article : Google Scholar

9 

Kume T: Ligand-Dependent notch signaling in vascular formation. Adv Exp Med Biol. 727:210–222. 2012.PubMed/NCBI View Article : Google Scholar

10 

Hori K, Sen A and Artavanis-Tsakonas S: Notch signaling at a glance. J Cell Sci. 126:2135–2140. 2013.PubMed/NCBI View Article : Google Scholar

11 

Caolo V, Molin DG and Post MJ: Notch regulation of hematopoiesis, endothelial precursor cells, and blood vessel formation: Orchestrating the vasculature. Stem Cells Int. 2012(805602)2012.PubMed/NCBI View Article : Google Scholar

12 

Zhan CY, Yuan TM, Sun Y and Yu HM: Early gestational intrauterine infection induces postnatal lung inflammation and arrests lung development in a rat model. J Matern Fetal Neonatal Med. 24:213–222. 2011.PubMed/NCBI View Article : Google Scholar

13 

Pan J, Zhan C, Yuan T, Wang W, Shen Y, Sun Y, Wu T, Gu W, Chen L and Yu H: Effects and molecular mechanisms of intrauterine infection/inflammation on lung development. Respir Res. 19(93)2018.PubMed/NCBI View Article : Google Scholar

14 

Uenishi GI, Jung HS, Kumar A, Park MA, Hadland BK, McLeod E, Raymond M, Moskvin O, Zimmerman CE, Theisen DJ, et al: NOTCH signaling specifies arterial-type definitive hemogenic endotheliumfrom human pluripotent stem cells. Nat Commun. 9(1828)2018.PubMed/NCBI View Article : Google Scholar

15 

Zhao H, Xu CN, Huang C, Jiang J and Li L: Notch1 signaling participates in the release of inflammatory mediators in mouse RAW264.7 cells via activating NF-κB pathway. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 33:1310–1315. 2017.PubMed/NCBI(In Chinese).

16 

Wang Y, Chen H, Li H, Zhang J and Gao Y: Effect of angiopoietin-like protein 4 on rat pulmonary microvascular endothelial cells exposed to LPS. Int J Mol Med. 32:568–576. 2013.PubMed/NCBI View Article : Google Scholar

17 

Zhou HS, Li M, Sui BD, Wei L, Hou R, Chen WS, Li Q, Bi SH, Zhang JZ and Yi DH: Lipopolysaccharide impairs permeability of pulmonary microvascular endothelial cells via connexin40. Microvasc Res. 115:58–67. 2018.PubMed/NCBI View Article : Google Scholar

18 

Zhang K, Wang P, Huang S, Wang X, Li T, Jin Y, Hehir M and Xu C: Different mechanism of LPS-induced calcium increase in human lung epithelial cell and microvascular endothelial cell: A cell culture study in a model for ARDS. Mol Biol Rep. 41:4253–4259. 2014.PubMed/NCBI View Article : Google Scholar

19 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

20 

Landry JS, Chan T, Lands L and Menzies D: Long-Term impact of bronchopulmonary dysplasia on pulmonary function. Can Respir J. 18:265–270. 2011.PubMed/NCBI View Article : Google Scholar

21 

Krebs LT, Xue Y, Norton CR, Shutter JR, Maguire M, Sundberg JP, Gallahan D, Closson V, Kitajewski J, Callahan R, et al: Notch signaling is essential for vascular morphogenesis in mice. Genes Dev. 14:1343–1352. 2000.PubMed/NCBI

22 

Uyttendaele H, Ho J, Rossant J and Kitajewski J: Vascular patterning defects associated with expression of activated notch4 in embryonic endothelium. Proc Natl Acad Sci USA. 98:5643–5648. 2001.PubMed/NCBI View Article : Google Scholar

23 

Gale NW, Dominguez MG, Noguera I, Pan L, Hughes V, Valenzuela DM, Murphy AJ, Adams NC, Lin HC, Holash J, et al: Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to major defects in arterial and vascular development. Proc Natl Acad Sci USA. 101:15949–15954. 2004.PubMed/NCBI View Article : Google Scholar

24 

Trindade A, Kumar SR, Scehnet JS, Lopes-da-Costa L, Becker J, Jiang W, Liu R, Gill PS and Duarte A: Overexpression of delta-like 4 induces arterialization and attenuates vessel formation in developing mouse embryos. Blood. 112:1720–1729. 2008.PubMed/NCBI View Article : Google Scholar

25 

Qiao LN, Xu HB, Shi K, Zhou TF, Hua YM and Liu HM: Role of notch signal in angiotensin II induced pulmonary vascular remodeling. Transl Pediatr. 2:5–13. 2013.PubMed/NCBI View Article : Google Scholar

26 

Muratore CS, Luks FI, Zhou Y, Harty M, Reichner J and Tracy TF: Endotoxin alters early fetal lung morphogenesis. J Surg Res. 155:225–230. 2009.PubMed/NCBI View Article : Google Scholar

27 

Kallapur SG, Bachurski CJ, Le Cras TD, Joshi SN, Ikegami M and Jobe AH: Vascular changes after intra-amniotic endotoxin in preterm lamb lungs. Am J Physiol Lung Cell Mol Physiol. 287:L1178–L1185. 2004.PubMed/NCBI View Article : Google Scholar

28 

Bhatt AJ, Pryhuber GS, Huyck H, Watkins RH, Metlay LA and Maniscalco WM: Disrupted pulmonary vasculature and decreased vascular endothelial growth factor, Flt-1, and TIE-2 in human infants dying with bronchopulmonary dysplasia. Am J Respir Crit Care Med. 164:1971–1980. 2001.PubMed/NCBI View Article : Google Scholar

29 

Hou Y, Liu M, Husted C, Chen C, Thiagarajan K, Johns JL, Rao SP and Alvira CM: Activation of the nuclear factor-κB pathway during postnatal lung inflammation preserves alveolarization by suppressing macrophage inflammatory protein-2. Am J Physiol Lung Cell Mol Physiol. 309:L593–L604. 2015.PubMed/NCBI View Article : Google Scholar

30 

Alvira CM: Nuclear factor-kappa-B signaling in lung development and disease: One pathway, numerousfunctions. Birth Defects Res A Clin Mol Teratol. 100:202–216. 2014.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team