Open Access

Runx3 is a key modulator during the epithelial-mesenchymal transition of alveolar type II cells in animal models of BPD

  • Authors:
    • Haiping Yang
    • Jianhua Fu
    • Li Yao
    • Ana Hou
    • Xindong Xue
  • View Affiliations

  • Published online on: September 14, 2017     https://doi.org/10.3892/ijmm.2017.3135
  • Pages: 1466-1476
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bronchopulmonary dysplasia (BPD) is a major challenge for premature infants; however, the underlying mechanisms remain unclear. We previously reported that epithelial-mesenchymal transition (EMT) in alveolar type II (AT2) epithelial cells influences the normal alveolar development process. In this study, we wished to examine whether Runx3 is an important factor for BPD by regulating EMT in AT2 cells. In vivo, animal models of BPD were established by placing newborn rats in hyperoxia tanks. Lung tissue and isolated AT2 cells were collected on different days following exposure to oxygen. The pathological changes in lung tissue, alveolar development and Runx3 expression were then investigated. In vitro, RLE-6TN cells were divided into 5 groups as follows: the cont­rol, Runx3, siRunx3, transforming growth factor-β1 (TGF-β1) and Runx3 + TGF-β1 groups, and the biomarkers of EMT were investigated. In the newborn rat model of BPD, Runx3 protein and mRNA levels in both lung tissue and BPD-derived AT2 cells were significantly lower than those in the control group. The correlation between Runx3 protein expression and pulmonary development indicators was analyzed; Runx3 expression positively correlated with the radial alveolar count (RAC) and the percentage of smooth muscle actin-positive secondary septa, but negatively correlated with alveolar wall thickness. EMT was observed in the RLE-6TN cells in which the Runx3 gene was knocked down and follwoing TGF-β1‑induced EMT stimulation; however, TGF-β1 failed to induce EMT in the RLE-6TN cells overexpressing Runx3. On the whole, our data indicte that low Runx3 levels may promote EMT, while high Runx3 levels inhibit TGF-β1-induced EMT. Therefore, we predict that low levels of Runx3 in BPD lung tissue may promote EMT in AT2 cells, thus affecting alveolar development.
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November-2017
Volume 40 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Yang H, Fu J, Yao L, Hou A and Xue X: Runx3 is a key modulator during the epithelial-mesenchymal transition of alveolar type II cells in animal models of BPD. Int J Mol Med 40: 1466-1476, 2017.
APA
Yang, H., Fu, J., Yao, L., Hou, A., & Xue, X. (2017). Runx3 is a key modulator during the epithelial-mesenchymal transition of alveolar type II cells in animal models of BPD. International Journal of Molecular Medicine, 40, 1466-1476. https://doi.org/10.3892/ijmm.2017.3135
MLA
Yang, H., Fu, J., Yao, L., Hou, A., Xue, X."Runx3 is a key modulator during the epithelial-mesenchymal transition of alveolar type II cells in animal models of BPD". International Journal of Molecular Medicine 40.5 (2017): 1466-1476.
Chicago
Yang, H., Fu, J., Yao, L., Hou, A., Xue, X."Runx3 is a key modulator during the epithelial-mesenchymal transition of alveolar type II cells in animal models of BPD". International Journal of Molecular Medicine 40, no. 5 (2017): 1466-1476. https://doi.org/10.3892/ijmm.2017.3135