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Hyperoxia arrests pulmonary development in newborn rats via disruption of endothelial tight junctions and downregulation of Cx40

  • Authors:
    • Chong Li
    • Jianhua Fu
    • Hongyu Liu
    • Haiping Yang
    • Li Yao
    • Kai You
    • Xindong Xue
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Emergency, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 61-67
    |
    Published online on: April 28, 2014
       https://doi.org/10.3892/mmr.2014.2192
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Abstract

This study investigated changes in vascular endothelial cell tight junction structure and the expression of the gene encoding connexin 40 (Cx40) at the early pneumonedema stage of hyperoxia‑induced bronchopulmonary dysplasia (BPD) in a newborn rat model. A total of 96 newborn rats were randomly assigned to one of the following two groups, the hyperoxia group (n=48) and the control group (n=48). A hyperoxia-induced BPD model was established for the first group, while rats in the control group were maintained under normoxic conditions. Extravasation of Evans Blue (EB) was measured; the severity of lung injury was assessed; a transmission electron microscope (TEM) was used to examine the vascular endothelial cell tight junction structures, and immunohistochemical assay, western blotting and reverse transcription-polymerase chain reaction (RT-PCR) were used to evaluate the expression of Cx40 at the mRNA and protein level. Our findings showed that injuries due to BPD are progressively intensified during the time-course of exposure to hyperoxic conditions. Pulmonary vascular permeability in the hyperoxia group reached the highest level at day 5, and was significantly higher compared to the control group. TEM observations demonstrated tight junctions between endothelial cells were extremely tight. In the hyperoxia group, no marked changes in the tight junction structure were found at days 1 and 3; paracellular gaps were visible between endothelial cells at days 5 and 7. Immunohistochemical staining revealed that the Cx40 protein is mainly expressed in the vascular endothelial cells of lung tissue. Western blotting and RT-PCR assays showed a gradual decrease in Cx40 expression, depending on the exposure time to hyperoxic conditions. However, the Cx40 mRNA level reached a trough at 5 days. Overall, our study demonstrated that exposure to hyperoxia damages the tight junction structures between vascular endothelial cells and downregulates Cx40. We therefore conclude that hyperoxia may participate in the regulation of pulmonary vascular endothelial permeability.
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1 

Bhandari A and Bhandari V: ‘New’ bronchopulmonary dysplasia: a clinical review. Clin Pulm Med. 18:137–143. 2011.

2 

Trembath A and Laughon MM: Predictors of bronchopulmonary dysplasia. Clin Perinatol. 39:585–601. 2012. View Article : Google Scholar

3 

Coalson JJ: Pathology of bronchopulmonary dysplasia. Semin Perinatol. 30:179–184. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Doyle LW, Faber B, Callanan C, Freezer N, Ford GW and Davis NM: Bronchopulmonary dysplasia in very low birth weight subjects and lung function in late adolescence. Pediatrics. 118:108–113. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Iles KE, Song W, Miller DW, Dickinson DA and Matalon S: Reactive species and pulmonary edema. Expert Rev Respir Med. 3:487–496. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Kolliputi N, Shaik RS and Waxman AB: The inflammasome mediates hyperoxia-induced alveolar cell permeability. J Immunol. 184:5819–5826. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Bhandari V and Elias JA: Cytokines in tolerance to hyperoxia-induced injury in the developing and adult lung. Free Radic Biol Med. 41:4–18. 2006. View Article : Google Scholar : PubMed/NCBI

8 

You K, Xu X, Fu J, Xu S, Yue X, Yu Z and Xue X: Hyperoxia disrupts pulmonary epithelial barrier in newborn rats via the deterioration of occluding and ZO-1. Respir Res. 13:362012. View Article : Google Scholar : PubMed/NCBI

9 

Jobe AH and Kallapur SG: Long term consequences of oxygen therapy in the neonatal period. Semin Fetal Neonatal Med. 15:230–235. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Barazzone C and White CW: Mechanisms of cell injury and death in hyperoxia: role of cytokines and Bcl-2 family proteins. Am J Respir Cell Mol Biol. 22:517–519. 2000. View Article : Google Scholar : PubMed/NCBI

11 

Crapo JD, Barry BE, Foscue HA and Shelburne J: Structural and biochemical changes in rat lungs occurring during exposures to lethal and adaptive doses of oxygen. Am Rev Respir Dis. 122:123–143. 1980.PubMed/NCBI

12 

Perkett EA and Klekamp JG: Vascular endothelial growth factor expression is decreased in rat lung following exposure to 24 or 48 hours of hyperoxia: implications for endothelial cell survival. Chest. 114:52S–53S. 1998. View Article : Google Scholar : PubMed/NCBI

13 

Saez JC, Berthoud VM, Branes MC, Martinez AD and Beyer EC: Plasma membrane channels formed by connexins: their regulation and functions. Physiol Rev. 83:1359–1400. 2003.PubMed/NCBI

14 

Ale-Aqha N, Albrecht C and Klotz LO: Loss of gap junctional intercellular communication in rat lung epithelial cells exposed to quartz particles. Biochem Biophys Res Commun. 390:44–47. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Rignault S, Haefliger JA, Waeber B, Liaudet L and Feihl F: Acute inflammation decrease the expression of connexin 40 in mouse lung. Shock. 28:78–85. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Elzarrad MK, Haroon A, Willecke K, Dobrowolski R, Gillespie MN and Al-Mehdi AB: Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium. BMC Med. 6:202008. View Article : Google Scholar : PubMed/NCBI

17 

Li Q, Zhang J, Wang W, et al: Connexin 40 modulates pulmonary permeability through gap junction channel in acute lung injury after thoracic gunshot wounds. J Trauma. 68:802–809. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Zhang J, Wang W, Sun J, et al: Gap junction channel modulates pulmonary vscular permeability through calcium in acute lung injury: an experimental study. Respiration. 80:236–245. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Matute-Bello G, Downey G, Moore BB, et al; Acute Lung Injury in Animals Study Group. An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 44:725–738. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Huang X and Zhao YY: Transgenic expression of FoxM1 promotes endothelial repair following lung injury induced by polymicrobial sepsis in mice. PLoS One. 7:e500942012. View Article : Google Scholar : PubMed/NCBI

21 

Coalson JJ, Winter VT, Siler-Khodr T and Yoder BA: Neonatal chronic lung disease in extremely immature baboons. Am J Respir Crit Care Med. 160:1333–1346. 1999. View Article : Google Scholar : PubMed/NCBI

22 

Ji W, Fu J, Nie H and Xue X: Expression and activity of epithelial sodium channel in hyperoxia-induced bronchopulmonary dysplasia in neonatal rats. Pediatr Int. 54:735–742. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Ben-Ari J, Makhoul IR, Dorio RJ, Buckley S, Warburton D and Walker SM: Cytokine response during hyperoxia: sequential production of pulmonary tumor necrosis factor and interleukin-6 in neonatal rats. Isr Med Assoc J. 2:365–369. 2000.PubMed/NCBI

24 

Auten RL and Davis JM: Oxygen toxicity and reactive oxygen species: the devil is in the details. Pediatr Res. 66:121–127. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Yucel O, Kunak ZI, Macit E, Gunal A, Gozubuyuk A, Gul H and Genc O: Protective efficiacy of taurine against pulmonary edema progression: experimental study. J Cardiothorac Surg. 3:572008. View Article : Google Scholar : PubMed/NCBI

26 

Doyle LW, Ehrenkranz RA and Halliday HL: Dexamethasone treatment in the first week of life for preventing bronchopulmonary dysplasia in preterm infants: a systematic review. Neonatology. 98:217–224. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Dani C, Cecchi A and Bertini G: Role of oxidative stress as physiopathologic factor in the preterm infant. Minerva Pediatr. 56:381–394. 2004.(in English, Italian).

28 

Yin Q, Nan H, Yan L, Huang X, Wang W, Cui G and Wei J: Alteration of tight junctions in pulmonary microvascular endothelial cells in bleomycin-treated rats. Exp Toxicol Pathol. 64:81–91. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Trovato-Salinaro A, Trovato-Salinaro A, Failla M, et al: Altered intercellular communication in lung fibroblast cultures from patients with idiopathic pulmonary fibrosis. Respir Res. 7:1222006. View Article : Google Scholar : PubMed/NCBI

30 

Simon AM, McWhorter AR, Chen H, Jackson CL and Ouellette Y: Decreased intercellular communication and connexin expression in mouse aortic endothelium during lipopolysaccharide-induced inflammation. J Vasc Res. 41:323–333. 2004. View Article : Google Scholar

31 

Wang L, Yin J, Nickles HT, et al: Hypoxic pulmonary vasoconstriction requires connexin 40-mediated endothelial signal conduction. J Clin Invest. 122:4218–4230. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Giepmans BN: Gap junctions and connexin-interacting proteins. Cardiovasc Res. 62:233–245. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Toyofuku T, Yabuki M, Otsu K, Kuzuya T, Hori M and Tada M: Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes. J Biol Chem. 273:12725–12731. 1998. View Article : Google Scholar : PubMed/NCBI

34 

Herve JC, Bourmeyster N and Sarrouilhe D: Diversity in protein-protein interactions of connexins: emerging roles. Biochim Biophys Acta. 1662:22–41. 2004. View Article : Google Scholar : PubMed/NCBI

35 

Valiunas V, Gemel J, Brink PR and Beyer EC: Gap junction channels formed by coexpressed connexin 40 and connexin 43. Am J Physiol Heart Circ Physiol. 281:H1675–H1689. 2001.PubMed/NCBI

36 

Nagasawa K, Chiba H, Fujita H, Kojima T, Saito T, Endo T and Sawada N: Possible involvement of gap junctions in the barrier function of tight junctions of brain and lung endothelial cells. J Cell Physiol. 208:123–132. 2006. View Article : Google Scholar : PubMed/NCBI

37 

Coalson JJ: Pathology of new bronchopulmonary dysplasia. Semin Neonatol. 8:73–81. 2003. View Article : Google Scholar

38 

Warner BB, Stuart LA, Papes RA and Wispé JR: Functional and pathological effects of prolonged hyperoxia in neonatal mice. Am J Physiol. 275:L110–L117. 1998.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li C, Fu J, Liu H, Yang H, Yao L, You K and Xue X: Hyperoxia arrests pulmonary development in newborn rats via disruption of endothelial tight junctions and downregulation of Cx40. Mol Med Rep 10: 61-67, 2014.
APA
Li, C., Fu, J., Liu, H., Yang, H., Yao, L., You, K., & Xue, X. (2014). Hyperoxia arrests pulmonary development in newborn rats via disruption of endothelial tight junctions and downregulation of Cx40. Molecular Medicine Reports, 10, 61-67. https://doi.org/10.3892/mmr.2014.2192
MLA
Li, C., Fu, J., Liu, H., Yang, H., Yao, L., You, K., Xue, X."Hyperoxia arrests pulmonary development in newborn rats via disruption of endothelial tight junctions and downregulation of Cx40". Molecular Medicine Reports 10.1 (2014): 61-67.
Chicago
Li, C., Fu, J., Liu, H., Yang, H., Yao, L., You, K., Xue, X."Hyperoxia arrests pulmonary development in newborn rats via disruption of endothelial tight junctions and downregulation of Cx40". Molecular Medicine Reports 10, no. 1 (2014): 61-67. https://doi.org/10.3892/mmr.2014.2192
Copy and paste a formatted citation
x
Spandidos Publications style
Li C, Fu J, Liu H, Yang H, Yao L, You K and Xue X: Hyperoxia arrests pulmonary development in newborn rats via disruption of endothelial tight junctions and downregulation of Cx40. Mol Med Rep 10: 61-67, 2014.
APA
Li, C., Fu, J., Liu, H., Yang, H., Yao, L., You, K., & Xue, X. (2014). Hyperoxia arrests pulmonary development in newborn rats via disruption of endothelial tight junctions and downregulation of Cx40. Molecular Medicine Reports, 10, 61-67. https://doi.org/10.3892/mmr.2014.2192
MLA
Li, C., Fu, J., Liu, H., Yang, H., Yao, L., You, K., Xue, X."Hyperoxia arrests pulmonary development in newborn rats via disruption of endothelial tight junctions and downregulation of Cx40". Molecular Medicine Reports 10.1 (2014): 61-67.
Chicago
Li, C., Fu, J., Liu, H., Yang, H., Yao, L., You, K., Xue, X."Hyperoxia arrests pulmonary development in newborn rats via disruption of endothelial tight junctions and downregulation of Cx40". Molecular Medicine Reports 10, no. 1 (2014): 61-67. https://doi.org/10.3892/mmr.2014.2192
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