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
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
November-2018 Volume 42 Issue 5

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
November-2018 Volume 42 Issue 5

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

Upregulated EFNB2 and EPHB4 promotes lung development in a nitrofen-induced congenital diaphragmatic hernia rat model

  • Authors:
    • Hao Liu
    • Xue Li
    • Wen Qian Yu
    • Cai Xia Liu
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology and Obstetrics, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning 110004, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2373-2382
    |
    Published online on: August 14, 2018
       https://doi.org/10.3892/ijmm.2018.3824
  • 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

Congenital diaphragmatic hernia (CDH) is a common congenital malformation associated with high mortality rates, mainly due to pulmonary hypoplasia and persistent pulmonary hypertension following birth. The present study aimed to investigate abnormal lung development in a rat CDH model, and examine temporal and spatial changes in the expression of ephrin type‑B receptor 4 (EPHB4) and ephrin‑B2 (EFNB2) during fetal lung development, to elucidate the role of these factors during lung morphogenesis. Pregnant rats received nitrofen on embryonic day (E) 8.5 to induce CDH, and fetal lungs were collected on E13.5, E15.5, E17.5, E19.5, and E21.5. The mean linear intercept (MLI) and mean alveolar number (MAN) were observed in fetal lung tissue at E21.5 following hematoxylin and eosin staining. E13.5 fetal lungs were cultured for 96 h in serum‑free medium and branch development was observed under a microscope. The gene and protein expression levels of EPHB4 and EFNB2 were assessed by reverse transcription‑quantitative polymerase chain reaction analysis, and immunoblotting and immunohistochemistry, respectively. The fetal rat lungs were treated with EFNB2 and the activity of key signaling pathways was assessed. The lung index (lung weight/body weight) at E21.5 was significantly lower in the CDH rats, compared with that in the control fetal rats. The MLI and MAN were also lower in the CDH group. The number of lung terminal buds at E13.5 (embryonic stage), and the lung‑explant perimeter and surface were all smaller in the CDH group rats than in the control group at the same age. Pulmonary hypoplasia was observed following 96 h of in vitro culture. No significant differences were found in the expression levels of EFNB2 and EPHB4 between the CDH and control groups at E13.5 (embryonic stage) or E15.5 (pseudoglandular stage), however, EFNB2 and EPHB4 were significantly upregulated at E17.5 (canalicular stage), and at E19.5 and E21.5 (saccular/alveolar stages). EFNB2 stimulated pulmonary branching and EFNB2 supplementation decreased the activity of p38, c‑Jun NH2‑terminal kinase, extracellular signal‑regulated kinase, and signal transducer and activator of transcription. The CDH fetal rats developed pulmonary dysplasia at an early stage of fetal pulmonary development. Upregulated expression of EFNB2 and EPHB4 was observed in the rat lung of nitrofen‑induced CDH, and the increased expression of EFNB2 promoted rat lung development in the nitrofen‑induced CDH model.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Torfs CP, Curry CJ, Bateson TF and Honoré LH: A population-based study of congenital diaphragmatic hernia. Teratology. 46:555–565. 1992. View Article : Google Scholar : PubMed/NCBI

2 

Skari H, Bjornland K, Haugen G, Egeland T and Emblem R: Congenital diaphragmatic hernia: A meta-analysis of mortality factors. J Pediatr Surg. 35:1187–1197. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Pober BR, Russell MK and Ackerman KG: Congenital Diaphragmatic Hernia Overview.

4 

van Loenhout RB, Tibboel D, Post M and Keijzer R: Congenital diaphragmatic hernia: Comparison of animal models and relevance to the human situation. Neonatology. 96:137–149. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Pober BR: Overview of epidemiology, genetics, birth defects, and chromosome abnormalities associated with CDH. Am J Med Genet C Semin Med Genet. 145C:158–171. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Peetsold MG, Heij HA, Kneepkens CM, Nagelkerke AF, Huisman J and Gemke RJ: The long-term follow-up of patients with a congenital diaphragmatic hernia: A broad spectrum of morbidity. Pediatr Surg Int. 25:1–17. 2009. View Article : Google Scholar

7 

Muratore CS, Kharasch V, Lund DP, Sheils C, Friedman S, Brown C, Utter S, Jaksic T and Wilson JM: Pulmonary morbidity in 100 survivors of congenital diaphragmatic hernia monitored in a multidisciplinary clinic. J Pediatr Surg. 36:133–140. 2001. View Article : Google Scholar

8 

Badillo A and Gingalewski C: Congenital diaphragmatic hernia: Treatment and outcomes. Semin Perinatol. 38:92–96. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Bargy F, Beaudoin S and Barbet P: Fetal lung growth in congenital diaphragmatic hernia. Fetal Diagn Ther. 21:39–44. 2006. View Article : Google Scholar

10 

Acker SN, Mandell EW, Sims-Lucas S, Gien J, Abman SH and Galambos C: Histologic identification of prominent intrapul-monary anastomotic vessels in severe congenital diaphragmatic hernia. J Pediatr. 166:178–183. 2015. View Article : Google Scholar

11 

Sluiter I, Reiss I, Kraemer U, Krijger Rd, Tibboel D and Rottier RJ: Vascular abnormalities in human newborns with pulmonary hypertension. Expert Rev Respir Med. 5:245–256. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Guilbert TW, Gebb SA and Shannon JM: Lung hypoplasia in the nitrofen model of congenital diaphragmatic hernia occurs early in development. Am J Physiol Lung Cell Mol Physiol. 279:L1159–L1171. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Hirai H, Maru Y, Hagiwara K, Nishida J and Takaku F: A novel putative tyrosine kinase receptor encoded by the eph gene. Science. 238:1717–1720. 1987. View Article : Google Scholar : PubMed/NCBI

14 

Pasquale EB: Eph-ephrin bidirectional signaling in physiology and disease. Cell. 133:38–52. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Klein R: Eph/ephrin signalling during development. Development. 139:4105–4109. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Kania A and Klein R: Mechanisms of ephrin-eph signalling in development, physiology and disease. Nat Rev Mol Cell Biol. 17:240–256. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Lisabeth EM, Falivelli G and Pasquale EB: Eph receptor signaling and ephrins. Cold Spring Harb Perspect Biol. 5:a0091592013. View Article : Google Scholar : PubMed/NCBI

18 

Cheng N, Brantley DM and Chen J: The ephrins and eph receptors in angiogenesis. Cytokine Growth Factor Rev. 13:75–85. 2002. View Article : Google Scholar

19 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar

20 

Downard CD, Jaksic T, Garza JJ, Dzakovic A, Nemes L, Jennings RW and Wilson JM: Analysis of an improved survival rate for congenital diaphragmatic hernia. J Pediatr Surg. 38:729–732. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Kinane TB: Lung development and implications for hypoplasia found in congenital diaphragmatic hernia. Am J Med Genet C Semin Med Genet. 145C:117–124. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Warburton D, Schwarz M, Tefft D, Flores-Delgado G, Anderson KD and Cardoso WV: The molecular basis of lung morphogenesis. Mech Dev. 92:55–81. 2000. View Article : Google Scholar : PubMed/NCBI

23 

Cardoso WV: Molecular regulation of lung development. Annu Rev Physiol. 63:471–494. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Groenman F, Unger S and Post M: The molecular basis for abnormal Human lung development. Biol Neonate. 87:164–177. 2005. View Article : Google Scholar

25 

Cardoso WV and Lü J: Regulation of early lung morphogenesis: Questions, facts and controversies. Development. 133:1611–1124. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Ware LB and Matthay MA: Keratinocyte and hepatocyte growth factors in the lung: Roles in lung development inflammation and repair. Am J Physiol Lung Cell Mol Physiol. 282:L924–L940. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Wang Y, Nakayama M, Pitulescu ME, Schmidt TS, Bochenek ML, Sakakibara A, Adams S, Davy A, Deutsch U, Lüthi U, et al: Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature. 465:483–486. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Vadivel A, van Haaften T, Alphonse RS, Rey-Parra GJ, Ionescu L, Haromy A, Eaton F, Michelakis E and Thébaud B: Critical role of the axonal guidance cue EphrinB2 in lung growth, angiogenesis, and repair. Am J Respir Crit Care Med. 185:564–574. 2012. View Article : Google Scholar

29 

Bennett KM, Afanador MD, Lal CV, Xu H, Persad E, Legan SK, Chenaux G, Dellinger M, Savani RC, Dravis C, et al: Ephrin-B2 reverse signaling increases α5β1 integrin mediated fibronectin deposition and reduces distal lung compliance. Am J Respir Cell Mol Biol. 49:680–687. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Sikkema AH, den Dunnen WF, Hulleman E, van Vuurden DG, Garcia-Manero G, Yang H, Scherpen FJ, Kampen KR, Hoving EW, Kamps EW, et al: EphB2 activity plays a pivotal role in pediatric medulloblastoma cell adhesion and invasion. Neuro Oncol. 14:1125–1135. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Nogueira-Silva C, Piairo P, Carvalho-Dias E, Veiga C, Moura RS and Correia-Pinto J: The role of glycoprotein 130 family of cytokines in fetal rat lung development. PLoS One. 8:e676072013. View Article : Google Scholar : PubMed/NCBI

32 

Nogueira-Silva C, Piairo P, Carvalho-Dias E, Peixoto FO, Moura RS and Correia-Pinto J: Leukemia inhibitory factor in rat fetal lung development: Expression and functional studies. PLoS One. 7:e305172012. View Article : Google Scholar : PubMed/NCBI

33 

Kling DE, Lorenzo HK, Trbovich AM, Kinane TB, Donahoe PK and Schnitzer JJ: MEK-1/2 inhibition reduces branching morphogenesis and causes mesenchymal cell apoptosis in fetal rat lungs. Am J Physiol Lung Cell Mol Physiol. 282:L370–L378. 2002. View Article : Google Scholar : PubMed/NCBI

34 

Piairo P, Moura RS, Nogueira-Silva C and Correia-Pinto J: The apelinergic system in the developing lung: Expression and signaling. Peptides. 32:2474–2483. 2011. View Article : Google Scholar : PubMed/NCBI

35 

Boucherat O, Nadeau V, Bérubé-Simard FA, Charron J and Jeannotte L: Crucial requirement of ERK/MAPK signaling in respiratory tract development. Development. 21:3197–3211. 2014. View Article : Google Scholar

36 

Boucherat O, Landry-Truchon K, Aoidi R, Houde N, Nadeau V, Charron J and Jeannotte L: Lung development requires an active ERK/MAPK pathway in the lung mesenchyme. Dev Dyn. 246:72–82. 2017. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu H, Li X, Yu WQ and Liu CX: Upregulated EFNB2 and EPHB4 promotes lung development in a nitrofen-induced congenital diaphragmatic hernia rat model. Int J Mol Med 42: 2373-2382, 2018.
APA
Liu, H., Li, X., Yu, W.Q., & Liu, C.X. (2018). Upregulated EFNB2 and EPHB4 promotes lung development in a nitrofen-induced congenital diaphragmatic hernia rat model. International Journal of Molecular Medicine, 42, 2373-2382. https://doi.org/10.3892/ijmm.2018.3824
MLA
Liu, H., Li, X., Yu, W. Q., Liu, C. X."Upregulated EFNB2 and EPHB4 promotes lung development in a nitrofen-induced congenital diaphragmatic hernia rat model". International Journal of Molecular Medicine 42.5 (2018): 2373-2382.
Chicago
Liu, H., Li, X., Yu, W. Q., Liu, C. X."Upregulated EFNB2 and EPHB4 promotes lung development in a nitrofen-induced congenital diaphragmatic hernia rat model". International Journal of Molecular Medicine 42, no. 5 (2018): 2373-2382. https://doi.org/10.3892/ijmm.2018.3824
Copy and paste a formatted citation
x
Spandidos Publications style
Liu H, Li X, Yu WQ and Liu CX: Upregulated EFNB2 and EPHB4 promotes lung development in a nitrofen-induced congenital diaphragmatic hernia rat model. Int J Mol Med 42: 2373-2382, 2018.
APA
Liu, H., Li, X., Yu, W.Q., & Liu, C.X. (2018). Upregulated EFNB2 and EPHB4 promotes lung development in a nitrofen-induced congenital diaphragmatic hernia rat model. International Journal of Molecular Medicine, 42, 2373-2382. https://doi.org/10.3892/ijmm.2018.3824
MLA
Liu, H., Li, X., Yu, W. Q., Liu, C. X."Upregulated EFNB2 and EPHB4 promotes lung development in a nitrofen-induced congenital diaphragmatic hernia rat model". International Journal of Molecular Medicine 42.5 (2018): 2373-2382.
Chicago
Liu, H., Li, X., Yu, W. Q., Liu, C. X."Upregulated EFNB2 and EPHB4 promotes lung development in a nitrofen-induced congenital diaphragmatic hernia rat model". International Journal of Molecular Medicine 42, no. 5 (2018): 2373-2382. https://doi.org/10.3892/ijmm.2018.3824
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