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Activation of Wnt/β‑Catenin‑p130/E2F4 promotes the differentiation of bone marrow‑derived mesenchymal stem cells into type II alveolar epithelial cells through cell cycle arrest

  • Authors:
    • Xiwen Zhang
    • Ming Xue
    • Airan Liu
    • Haibo Qiu
    • Fengmei Guo
  • View Affiliations / Copyright

    Affiliations: Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 330
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    Published online on: May 18, 2023
       https://doi.org/10.3892/etm.2023.12029
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Abstract

The results of our previous study demonstrated that activation of the Wnt/β‑catenin pathway increased the differentiation of mesenchymal stem cells (MSCs) into type II alveolar epithelial (AT II) cells; however, the specific mechanisms remain unclear. The present study aimed to evaluate the role of Wnt/β‑catenin‑p130/E2F transcription factor 4 (E2F4) in regulating the differentiation of mouse MSCs (mMSCs) into AT II cells, and to determine the specific mechanisms. mMSCs with p130 or E2F4 overexpression were constructed using lentiviral vectors. Differentiation of mMSCs into AT II cells was promoted using a modified coculture system with murine lung epithelial‑12 cells incubated in small airway growth medium for 7‑14 days. The differentiation efficiency was detected using immunofluorescence, western blot analysis and transmission electron microscopy. To detect the association between the canonical Wnt pathway and p130/E2F4, 4 mmol/l lithium chloride (LiCl) or 200 ng/ml Dickkopf‑related protein 1 (DKK‑1) was also added to the coculture system. Following differentiation, the cell cycle of mMSCs was evaluated using flow cytometry. The results of the present study demonstrated that surfactant protein C (SP‑C) protein expression was higher in the p130 overexpression (MSC‑p130) and E2F4 overexpression (MSC‑E2F4) groups compared with the normal control mMSCs group following differentiation into AT II cells. Similar results for SP‑C protein expression and lamellar body‑like structures were also observed using immunofluorescence analysis and electron microscopy. Following the addition of LiCl into the coculture system for activation of the Wnt/β‑catenin signaling pathway, phosphorylated (p)‑p130/p130 was slightly decreased at 7 days and E2F4 was increased both at 7 and 14 days in mMSCs. Furthermore, the p‑p130/p130 ratio was significantly increased at 14 days and E2F4 was decreased both at 7 and 14 days following DKK‑1‑mediated inhibition of the Wnt pathway. The results of the present study demonstrated that the numbers of cells in G1 and S phases were increased following activation of the Wnt pathway and decreased following Wnt pathway inhibition. However, the number of cells in G1 phase was increased following the differentiation of mMSCs overexpressing p130 or E2F4. Therefore, the results of the present study revealed that the canonical Wnt signaling pathway may affect the differentiation of MSCs into AT II cells via regulation of downstream p130/E2F4. The specific mechanisms may be associated with G1 phase extension in the cell cycle of MSCs.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang X, Xue M, Liu A, Qiu H and Guo F: Activation of Wnt/β‑Catenin‑p130/E2F4 promotes the differentiation of bone marrow‑derived mesenchymal stem cells into type II alveolar epithelial cells through cell cycle arrest. Exp Ther Med 26: 330, 2023.
APA
Zhang, X., Xue, M., Liu, A., Qiu, H., & Guo, F. (2023). Activation of Wnt/β‑Catenin‑p130/E2F4 promotes the differentiation of bone marrow‑derived mesenchymal stem cells into type II alveolar epithelial cells through cell cycle arrest. Experimental and Therapeutic Medicine, 26, 330. https://doi.org/10.3892/etm.2023.12029
MLA
Zhang, X., Xue, M., Liu, A., Qiu, H., Guo, F."Activation of Wnt/β‑Catenin‑p130/E2F4 promotes the differentiation of bone marrow‑derived mesenchymal stem cells into type II alveolar epithelial cells through cell cycle arrest". Experimental and Therapeutic Medicine 26.1 (2023): 330.
Chicago
Zhang, X., Xue, M., Liu, A., Qiu, H., Guo, F."Activation of Wnt/β‑Catenin‑p130/E2F4 promotes the differentiation of bone marrow‑derived mesenchymal stem cells into type II alveolar epithelial cells through cell cycle arrest". Experimental and Therapeutic Medicine 26, no. 1 (2023): 330. https://doi.org/10.3892/etm.2023.12029
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang X, Xue M, Liu A, Qiu H and Guo F: Activation of Wnt/β‑Catenin‑p130/E2F4 promotes the differentiation of bone marrow‑derived mesenchymal stem cells into type II alveolar epithelial cells through cell cycle arrest. Exp Ther Med 26: 330, 2023.
APA
Zhang, X., Xue, M., Liu, A., Qiu, H., & Guo, F. (2023). Activation of Wnt/β‑Catenin‑p130/E2F4 promotes the differentiation of bone marrow‑derived mesenchymal stem cells into type II alveolar epithelial cells through cell cycle arrest. Experimental and Therapeutic Medicine, 26, 330. https://doi.org/10.3892/etm.2023.12029
MLA
Zhang, X., Xue, M., Liu, A., Qiu, H., Guo, F."Activation of Wnt/β‑Catenin‑p130/E2F4 promotes the differentiation of bone marrow‑derived mesenchymal stem cells into type II alveolar epithelial cells through cell cycle arrest". Experimental and Therapeutic Medicine 26.1 (2023): 330.
Chicago
Zhang, X., Xue, M., Liu, A., Qiu, H., Guo, F."Activation of Wnt/β‑Catenin‑p130/E2F4 promotes the differentiation of bone marrow‑derived mesenchymal stem cells into type II alveolar epithelial cells through cell cycle arrest". Experimental and Therapeutic Medicine 26, no. 1 (2023): 330. https://doi.org/10.3892/etm.2023.12029
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