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SOX4 arrests lung development in rats with hyperoxia‑induced bronchopulmonary dysplasia by controlling EZH2 expression

  • Authors:
    • Bingting Pan
    • Xindong Xue
    • Dan Zhang
    • Mengyun Li
    • Jianhua Fu
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
    Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1691-1698
    |
    Published online on: October 3, 2017
       https://doi.org/10.3892/ijmm.2017.3171
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Abstract

Bronchopulmonary dysplasia (BPD) is currently the most common severe complication in premature infants and is characterized by the arrest of alveolar and vascular growth. Alveolar type II cells play an important role in the pathological foundation of BPD. An association of BPD with epithelial‑to‑mesenchymal transition (EMT) in type II cells exposed to hyperoxia was previously identified. SOX4, a transcription factor that is indispensable to embryogenesis, including lung development, participates in regulating EMT and cell survival, affecting tumorigenesis. The aim of the present study was to investigate the involvement of SOX4 in the occurrence of BPD, which, to the best of our knowledge, has not been previously determined. For this purpose, newborn rats were randomly divided into two treatment groups: The model group was exposed to hyperoxia (80-85% O2), while the control group was kept under normoxic conditions (21% O2). Lung tissues were collected on postnatal days 1, 3, 7, 14 and 21 and morphological changes in the lungs were examined by hematoxylin and eosin staining. The location of SOX4 in type II cells was detected by double immunofluorescence. The expression of SOX4 and enhancer of zeste homolog 2 (EZH2) in type II cells and lung tissues were detected by immunochemistry, western blotting and quantitative polymerase chain reaction analysis. The results demonstrated that, compared with the control group, the radial alveolar count decreased rapidly in the model group, accompanied by increased mean alveolar diameter and alveolar septal thickness. SOX4 and EZH2 were highly expressed in type II cells exposed to hyperoxia. However, in total lung tissues, SOX4 and EZH2 expression was profoundly decreased in the early stages and increased in the late stages following exposure to hyperoxia. The expression of the EZH2 protein was positively correlated with that of the SOX4 protein. In conclusion, at the alveolar stage, which is a critical period after birth for lung development, hyperoxia induced dysregulation of SOX4 and EZH2 in rat lungs, indicating that SOX4 may contribute to the disruption of lung development in BPD by regulating EZH2 expression.
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View References

1 

Baker CD and Abman SH: Impaired pulmonary vascular development in bronchopulmonary dysplasia. Neonatology. 107:344–351. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Kinsella JP, Greenough A and Abman SH: Bronchopulmonary dysplasia. Lancet. 367:1421–1431. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Baraldi E and Filippone M: Chronic lung disease after premature birth. N Engl J Med. 357:1946–1955. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Bhandari V: Hyperoxia-derived lung damage in preterm infants. Semin Fetal Neonatal Med. 15:223–229. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Lamouille S, Xu J and Derynck R: Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 15:178–196. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Yang H, Fu J, Xue X, Yao L, Qiao L, Hou A, Jin L and Xing Y: Epithelial-mesenchymal transitions in bronchopulmonary dysplasia of newborn rats. Pediatr Pulmonol. 49:1112–1123. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Zhu Y, Fu J, Yang H, Pan Y, Yao L and Xue X: Hyperoxia-induced methylation decreases RUNX3 in a newborn rat model of bronchopulmonary dysplasia. Respir Res. 16:752015. View Article : Google Scholar : PubMed/NCBI

8 

Wegner M: From head to toes: The multiple facets of Sox proteins. Nucleic Acids Res. 27:1409–1420. 1999. View Article : Google Scholar : PubMed/NCBI

9 

Vervoort SJ, van Boxtel R and Coffer PJ: The role of SRY-related HMG box transcription factor 4 (SOX4) in tumorigenesis and metastasis: Friend or foe? Oncogene. 32:3397–3409. 2013. View Article : Google Scholar

10 

Tiwari N, Tiwari VK, Waldmeier L, Balwierz PJ, Arnold P, Pachkov M, Meyer-Schaller N, Schübeler D, van Nimwegen E and Christofori G: Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming. Cancer Cell. 23:768–783. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Hasegawa S, Nagano H, Konno M, Eguchi H, Tomokuni A, Tomimaru Y, Asaoka T, Wada H, Hama N, Kawamoto K, et al: A crucial epithelial to mesenchymal transition regulator, Sox4/Ezh2 axis is closely related to the clinical outcome in pancreatic cancer patients. Int J Oncol. 48:145–152. 2016. View Article : Google Scholar

12 

Emery JL and Mithal A: The number of alveoli in the terminal respiratory unit of man during late intrauterine life and childhood. Arch Dis Child. 35:544–547. 1960. View Article : Google Scholar : PubMed/NCBI

13 

Jobe AH: The new bronchopulmonary dysplasia. Curr Opin Pediatr. 23:167–172. 2011. View Article : Google Scholar

14 

Crapo JD, Barry BE, Gehr P, Bachofen M and Weibel ER: Cell number and cell characteristics of the normal human lung. Am Rev Respir Dis. 126:332–337. 1982.PubMed/NCBI

15 

Castranova V, Rabovsky J, Tucker JH and Miles PR: The alveolar type II epithelial cell: A multifunctional pneumocyte. Toxicol Appl Pharmacol. 93:472–483. 1988. View Article : Google Scholar : PubMed/NCBI

16 

Hou A, Fu J, Yang H, Zhu Y, Pan Y, Xu S and Xue X: Hyperoxia stimulates the transdifferentiation of type II alveolar epithelial cells in newborn rats. Am J Physiol Lung Cell Mol Physiol. 308:L861–L872. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Xu W, Xu B, Zhao Y, Yang N, Liu C, Wen G and Zhang B: Wnt5a reverses the inhibitory effect of hyperoxia on transdifferentiation of alveolar epithelial type II cells to type I cells. J Physiol Biochem. 71:823–838. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Pain M, Bermudez O, Lacoste P, Royer PJ, Botturi K, Tissot A, Brouard S, Eickelberg O and Magnan A: Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype. Eur Respir Rev. 23:118–130. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Lee JM, Shin JO, Cho KW, Hosoya A, Cho SW, Lee YS, Ryoo HM, Bae SC and Jung HS: Runx3 is a crucial regulator of alveolar differentiation and lung tumorigenesis in mice. Differentiation. 81:261–268. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Wang C, Liu X, Chen Z, Huang H, Jin Y, Kolokythas A, Wang A, Dai Y, Wong DT and Zhou X: Polycomb group protein EZH2-mediated E-cadherin repression promotes metastasis of oral tongue squamous cell carcinoma. Mol Carcinog. 52:229–236. 2013. View Article : Google Scholar

21 

Penzo-Méndez AI: Critical roles for SoxC transcription factors in development and cancer. Int J Biochem Cell Biol. 42:425–428. 2010. View Article : Google Scholar :

22 

Dy P, Penzo-Méndez A, Wang H, Pedraza CE, Macklin WB and Lefebvre V: The three SoxC proteins - Sox4, Sox11 and Sox12 - exhibit overlapping expression patterns and molecular properties. Nucleic Acids Res. 36:3101–3117. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Hoser M, Potzner MR, Koch JM, Bösl MR, Wegner M and Sock E: Sox12 deletion in the mouse reveals nonreciprocal redundancy with the related Sox4 and Sox11 transcription factors. Mol Cell Biol. 28:4675–4687. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Maeda Y, Davé V and Whitsett JA: Transcriptional control of lung morphogenesis. Physiol Rev. 87:219–244. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Wang D, Hao T, Pan Y, Qian X and Zhou D: Increased expression of SOX4 is a biomarker for malignant status and poor prognosis in patients with non-small cell lung cancer. Mol Cell Biochem. 402:75–82. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Medina PP, Castillo SD, Blanco S, Sanz-Garcia M, Largo C, Alvarez S, Yokota J, Gonzalez-Neira A, Benitez J, Clevers HC, et al: The SRY-HMG box gene, SOX4, is a target of gene amplification at chromosome 6p in lung cancer. Hum Mol Genet. 18:1343–1352. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Vervoort SJ, Lourenço AR, van Boxtel R and Coffer PJ: SOX4 mediates TGF-β-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition. PLoS One. 8:e532382013. View Article : Google Scholar

28 

Parvani JG and Schiemann WP: Sox4, EMT programs, and the metastatic progression of breast cancers: Mastering the masters of EMT. Breast Cancer Res. 15:R722013. View Article : Google Scholar : PubMed/NCBI

29 

Cao Q, Yu J, Dhanasekaran SM, Kim JH, Mani RS, Tomlins SA, Mehra R, Laxman B, Cao X, Yu J, et al: Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene. 27:7274–7284. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Hu Y, Liu X, Zhang H, Fu J and Xue X: dynamic changes of Bax/Bcl-2 expression in lung tissue and fibroblasts of neonatal rats after inhaling high concentration oxygen. J Appl Clin Pediatr. 26:589–592. 2011.

31 

Zhou Y, Wang X, Huang Y, Chen Y, Zhao G, Yao Q, Jin C, Huang Y, Liu X and Li G: Downregulated SOX4 expression suppresses cell proliferation, metastasis and induces apoptosis in Xuanwei female lung cancer patients. J Cell Biochem. 116:1007–1018. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Hur W, Rhim H, Jung CK, Kim JD, Bae SH, Jang JW, Yang JM, Oh ST, Kim DG, Wang HJ, et al: SOX4 overexpression regulates the p53-mediated apoptosis in hepatocellular carcinoma: Clinical implication and functional analysis in vitro. Carcinogenesis. 31:1298–1307. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Xie L, Zhang Z, Tan Z, He R, Zeng X, Xie Y, Li S, Tang G, Tang H and He X: MicroRNA-124 inhibits proliferation and induces apoptosis by directly repressing EZH2 in gastric cancer. Mol Cell Biochem. 392:153–159. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Kage H and Borok Z: EMT and interstitial lung disease: A mysterious relationship. Curr Opin Pulm Med. 18:517–523. 2012.PubMed/NCBI

35 

Pan X, Zhao J, Zhang WN, Li HY, Mu R, Zhou T, Zhang HY, Gong WL, Yu M, Man JH, et al: Induction of SOX4 by DNA damage is critical for p53 stabilization and function. Proc Natl Acad Sci USA. 106:3788–3793. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Pan B, Xue X, Zhang D, Li M and Fu J: SOX4 arrests lung development in rats with hyperoxia‑induced bronchopulmonary dysplasia by controlling EZH2 expression. Int J Mol Med 40: 1691-1698, 2017.
APA
Pan, B., Xue, X., Zhang, D., Li, M., & Fu, J. (2017). SOX4 arrests lung development in rats with hyperoxia‑induced bronchopulmonary dysplasia by controlling EZH2 expression. International Journal of Molecular Medicine, 40, 1691-1698. https://doi.org/10.3892/ijmm.2017.3171
MLA
Pan, B., Xue, X., Zhang, D., Li, M., Fu, J."SOX4 arrests lung development in rats with hyperoxia‑induced bronchopulmonary dysplasia by controlling EZH2 expression". International Journal of Molecular Medicine 40.6 (2017): 1691-1698.
Chicago
Pan, B., Xue, X., Zhang, D., Li, M., Fu, J."SOX4 arrests lung development in rats with hyperoxia‑induced bronchopulmonary dysplasia by controlling EZH2 expression". International Journal of Molecular Medicine 40, no. 6 (2017): 1691-1698. https://doi.org/10.3892/ijmm.2017.3171
Copy and paste a formatted citation
x
Spandidos Publications style
Pan B, Xue X, Zhang D, Li M and Fu J: SOX4 arrests lung development in rats with hyperoxia‑induced bronchopulmonary dysplasia by controlling EZH2 expression. Int J Mol Med 40: 1691-1698, 2017.
APA
Pan, B., Xue, X., Zhang, D., Li, M., & Fu, J. (2017). SOX4 arrests lung development in rats with hyperoxia‑induced bronchopulmonary dysplasia by controlling EZH2 expression. International Journal of Molecular Medicine, 40, 1691-1698. https://doi.org/10.3892/ijmm.2017.3171
MLA
Pan, B., Xue, X., Zhang, D., Li, M., Fu, J."SOX4 arrests lung development in rats with hyperoxia‑induced bronchopulmonary dysplasia by controlling EZH2 expression". International Journal of Molecular Medicine 40.6 (2017): 1691-1698.
Chicago
Pan, B., Xue, X., Zhang, D., Li, M., Fu, J."SOX4 arrests lung development in rats with hyperoxia‑induced bronchopulmonary dysplasia by controlling EZH2 expression". International Journal of Molecular Medicine 40, no. 6 (2017): 1691-1698. https://doi.org/10.3892/ijmm.2017.3171
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