Open Access

Overexpression of the hyperplasia suppressor gene inactivates airway fibroblasts obtained from a rat model of chronic obstructive pulmonary disease by inhibiting the Wnt signaling pathway

  • Authors:
    • Zhenghang Ge
    • Yi Yang
    • Xun Zhou
    • Jun Zhang
    • Bo Li
    • Xinxing Wang
    • Xian Luo
  • View Affiliations

  • Published online on: July 15, 2019     https://doi.org/10.3892/mmr.2019.10504
  • Pages: 2754-2762
  • Copyright: © Ge et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the effects of hyperplasia suppressor gene (HSG) overexpression on the activation of airway fibroblasts in a rat model of chronic obstructive pulmonary disease (COPD) and assess the underlying molecular mechanisms. The rat model of COPD was established by injection of papain and confirmed by hematoxylin and eosin staining. Airway fibroblasts were identified using immunofluorescence, and HSG expression was facilitated by an HSG vector. Cell viability, apoptosis and the levels of matrix metallopeptidase‑9 (MMP‑9), platelet‑derived growth factor (PDGF), and transforming growth factor‑β1 (TGF‑β1) were measured via Cell Counting Kit‑8, flow cytometry and ELISA analyses, respectively, and potential mechanisms were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting. Airway fibroblasts from COPD rats were isolated and identified based on vimentin expression. Compared with the control group, HSG overexpression reduced cell viability, promoted apoptosis, and reduced the protein levels of TGF‑β1, MMP‑9 and PDGF. Additionally, HSG overexpression reduced β‑catenin and Ras homology family member A (RhoA) expression at both the mRNA and protein levels. Conversely, Wnt signaling pathway agonists lithium chloride (LiCl) and 4‑ethyl‑5,6‑dihydro‑5‑methyl‑​(1,3)dioxolo(4,5‑j)phenanthridine (HLY78), significantly reduced the effects of HSG overexpression (P<0.05 vs. HSG). Cell viability in the HSG + LiCl and HSG + HLY78 groups was increased, whereas apoptosis was reduced compared with HSG treatment alone. The protein levels of TGF‑β1, MMP‑9 and PDGF were also decreased in the HSG + LiCl and HSG + HLY78 groups compared with the HSG group (P<0.05). Furthermore, the expression of β‑catenin and RhoA was higher in the HSG + LiCl and HSG + HLY78 groups compared with the HSG group (P<0.05). Collectively, the results indicated that HSG overexpression inactivated airway fibroblasts from COPD by inhibiting the Wnt signaling pathway.

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Copy and paste a formatted citation
APA
Ge, Z., Yang, Y., Zhou, X., Zhang, J., Li, B., Wang, X., & Luo, X. (2019). Overexpression of the hyperplasia suppressor gene inactivates airway fibroblasts obtained from a rat model of chronic obstructive pulmonary disease by inhibiting the Wnt signaling pathway. Molecular Medicine Reports, 20, 2754-2762. https://doi.org/10.3892/mmr.2019.10504
MLA
Ge, Z., Yang, Y., Zhou, X., Zhang, J., Li, B., Wang, X., Luo, X."Overexpression of the hyperplasia suppressor gene inactivates airway fibroblasts obtained from a rat model of chronic obstructive pulmonary disease by inhibiting the Wnt signaling pathway". Molecular Medicine Reports 20.3 (2019): 2754-2762.
Chicago
Ge, Z., Yang, Y., Zhou, X., Zhang, J., Li, B., Wang, X., Luo, X."Overexpression of the hyperplasia suppressor gene inactivates airway fibroblasts obtained from a rat model of chronic obstructive pulmonary disease by inhibiting the Wnt signaling pathway". Molecular Medicine Reports 20, no. 3 (2019): 2754-2762. https://doi.org/10.3892/mmr.2019.10504