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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Background The effects of Ardisia japonica (AJ) on airway remodeling in chronic obstructive pulmonary disease (COPD) rats, and the mechanisms have not been verified. This study aimed to investigate the effects of a Miao medicine, AJ on airway remodeling in COPD rats, and to assess the mechanisms.Methods COPD model was produced by cigarette smoke and intratracheal injection of lipopolysaccharide (LPS). The experiments were divided into a normal group, a COPD group, different doses of AJ treatment groups and a positive control group. After treatments, matrix metalloprotein (MMP)-9, platelet derived growth factor (PDGF) and transforming growth factor-β1 (TGF-β1) levels in inferior lobes of the right lung tissues were detected by ELISA. Expression of Wnt signaling pathway was detected by immunohistochemistry and Western blotting. To verify the function of Wnt signaling pathway in airway remodeling, airway fibroblasts obtained from COPD rats were treated with Wnt signaling pathway agonists. The cell proliferation, apoptosis, and MMP-9, PDGF, TGF-β1 levels were determined.Results The pathological changes of COPD were confirmed by haematoxylin eosin (H&E) staining. MMP-9, PDGF and TGF-β1 levels were promoted in COPD rats, which were significantly reduced by different doses of AJ treatment. Importantly, components of Wnt signaling pathway, including Wnt5a, β-catenin and RhoA were up-regulated in COPD model, which were also significantly reduced by treatment with different doses of AJ. The airway fibroblasts were obtained from COPD rats and verified based on vimentin expression. Wnt signaling pathway agonists, lithium chloride (Licl), 4-Ethyl-5,6-Dihydro-5-methyl-[1, 3] dioxolo[4,5-j] phenanthridine (HLY78), TPA and epidermal growth factor (EGF) promoted cell proliferation, reduced apoptosis, and promoted MMP-9, PDGF and TGF-β1 levels.Conclusions Our data implicated that AJ could prevent airway remodeling in COPD rats, likely via depressing Wnt signaling pathway.