Ac-SDKP suppresses epithelial–mesenchymal transition in A549 cells via HSP27 signaling

Deng, Haijing; Fang, Yang; Xu, Hong; Sun, Yunbo; Xue, Xinxin; Du, Shipu; Wang, Xiaojun; Li, Shifeng; Liu, Yan; Wang, Ruimin

doi:10.1016/j.yexmp.2014.07.003

Cited by 16 publications

(13 citation statements)

References 32 publications

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“…Accordingly, it was previously demonstrated that Ac-SDKP can inhibit the myofibroblast differentiation of human fetal lung fibroblasts (MRC-5) cells induced by Ang II [24]. Furthermore, it was shown that Ac-SDKP suppresses epithelial-mesenchymal transition in A549 cells via HSP27 signaling [25]. Since effective IPF therapies should be focused on halting the fibroblast/myofibroblast differentiation process, and consequently abnormal tissue remodeling as well as excessive accumulation of extracellular matrix, we propose Ac-SDKP as a valid putative drug for lung fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Preventive and therapeutic effects of thymosin β4 N-terminal fragment Ac-SDKP in the bleomycin model of pulmonary fibrosis

et al. 2016

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In this study, the bleomycin model of pulmonary fibrosis was utilized to investigate putative anti-fibrotic activity of Ac-SDKP in vivo. Male CD-1 mice received intra-tracheal bleomycin (BLEO, 1 mg/kg) instillation in the absence or presence of Ac-SDKP (a dose of 0.6 mg/kg delivered intra-peritoneally on the day of BLEO treatment, d0, followed by bi-weekly additional doses). To evaluate therapeutic effects in a subset of mice, Ac-SDKP was administered one week after BLEO instillation (d7). Animals were sacrificed at one, two, or three weeks later. Measurement of fluid and collagen content in the lung, Broncho Alveolar Lavage Fluid (BALF) analysis, lung histology, immunohistochemistry (IHC), and molecular analysis were performed. Compared to BLEO-treated mice, animals that received also Ac-SDKP (at both d0 and d7) had significantly decreased mortality, weight loss, inflammation (edema, and leukocyte lung infiltration), lung damage (histological evidence of lung injury), and fibrosis (collagen histological staining and soluble collagen content in the lung) at up to 21 days. Moreover, IHC and quantitative RT-PCR results demonstrated a significant decrease in BLEO-induced IL-17 and TGF-β expression in lung tissue. Importantly, α-SMA expression, the hallmark of myofibroblast differentiation, was also decreased. This is the first report showing not only a preventive protective role of Ac-SDKP but also its significant therapeutic effects in the bleomycin model of pulmonary fibrosis, thus supporting further preclinical and clinical studies.

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Section: Discussionmentioning

confidence: 99%

Preventive and therapeutic effects of thymosin β4 N-terminal fragment Ac-SDKP in the bleomycin model of pulmonary fibrosis

et al. 2016

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“…In vitro experiments have also demonstrated inhibition of epithelial-to-mesenchymal transition in tissue culture [29]. Mineralocorticoid receptor antagonists have been demonstrated to modulate Gal-3 expression after acute myocardial infarction [30] and to prevent aldosterone-salt induced cardiac hypertrophy, dysfunction, and fibrosis [31].…”

Section: Discussionmentioning

confidence: 99%

Galectin-3 is a marker of myocardial and vascular fibrosis in Kawasaki disease patients with giant aneurysms

Numano

Shimizu

Jimenez-Fernandez

et al. 2015

International Journal of Cardiology

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“…Type I and III collagen are essential ECM components that reflect the differentiation extent of myofibroblasts (40)(41)(42)(43). In our previous studies, we found that 5 ng/ml TGF-β1 was able to successfully induce the transition of A549 human alveolar type II epithelial cells to myofibroblasts, accompanied with upregulation of type I and III collagen expression (13). In A549 cells transfected with HSP27-interfering plasmid, the expression of type I and III collagen was downregulated by TGF-β1 stimulation, which suggested that HSP27 is a factor that may induce fibrosis in the transition of TGF-β1-induced A549 human alveolar type II epithelial cells to myofibroblasts.…”

Section: Discussionmentioning

confidence: 93%

“…Transforming growth factor-β1 (TGF-β1) is an important transforming growth factor associated with fibrosis in vitro and in vivo (11,12). A previous study by the authors revealed that TGF-β1 may induce A549 human alveolar type II epithelial cells to differentiate into myofibroblasts (13). In order to investigate the effect of HSP27 on the differentiation of A549 human alveolar type II epithelial cell line into myofibroblasts and collagen synthesis, the current study used liposome transfection to transfect A549 human alveolar type II epithelial cell line and determined the optimal liposome:plasmid ratio and the best interference sequence.…”

Section: Introductionmentioning

confidence: 99%

Effect of liposome‑mediated HSP27 transfection on collagen synthesis in alveolar type II epithelial cells

et al. 2018

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To investigate the effect of liposome Lipofectamine® 2000‑mediated HSP27 plasmid transfection in A549 human alveolar type II epithelial cell line on collagen synthesis during transforming growth factor‑β1 (TGF‑β1)‑induced type II epithelial cell transition to myofibroblasts. Cells were transfected with varying ratios of the Lipofectamine® 2000‑mediated heat shock protein 27 (HSP27) plasmid and the transfection efficiency was determined using flow cytometry. The maximum transfection efficacy was confirmed by laser confocal microscopy. HSP gene expression and the most efficient HSP27 plasmid were determined using reverse transcription‑quantitative polymerase chain reaction. Western blot analysis was used to examine HSP27 and collagen expression levels. With a transfection efficiency of 83%, the 8 µg:20 µl ratio of liposome: Plasmid had the highest transfection levels. Among the four different interference sequences in the HSP27 plasmid, the D sequence had the highest interference effect with 70% silencing of the HSP27 gene. The expression of type I and III collagen in TGF‑β1‑induced transition of A549 human alveolar type II epithelial cell line to myofibroblasts was significantly downregulated by the successful transfection with HSP27‑interfering plasmid. The expression of type I and III collagen in the TGF‑β1‑induced transition of A549 cells to myofibroblasts was significantly downregulated by transfection of A549 cells with HSP27 plasmid D‑interfering sequence and optimal ratio of Lipofectamine® 2000 and HSP27 plasmid.

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Ac-SDKP suppresses epithelial–mesenchymal transition in A549 cells via HSP27 signaling

Cited by 16 publications

References 32 publications

Preventive and therapeutic effects of thymosin β4 N-terminal fragment Ac-SDKP in the bleomycin model of pulmonary fibrosis

Preventive and therapeutic effects of thymosin β4 N-terminal fragment Ac-SDKP in the bleomycin model of pulmonary fibrosis

Galectin-3 is a marker of myocardial and vascular fibrosis in Kawasaki disease patients with giant aneurysms

Effect of liposome‑mediated HSP27 transfection on collagen synthesis in alveolar type II epithelial cells

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