LSC - 2020 - Epithelial-mesenchymal transition induced by cigarette smoke in lung epithelial cells is associated with metabolic reprogramming and senescence

2020 ◽  
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Epithelial Mesenchymal Transition ◽  
Lung Epithelial Cells ◽  
Metabolic Reprogramming ◽  
Mesenchymal Transition ◽  
Lung Epithelial

scholarly journals Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells

2021 ◽  
Vol 22 (21) ◽  
pp. 12069
Author(s):  
Tzu-Yin Chen ◽  
Chia-Hao Liu ◽  
Tsung-Hsien Chen ◽  
Mei-Ru Chen ◽  
Shan-Wen Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Epithelial Mesenchymal Transition ◽  
Cigarette Smoke Extract ◽  
Lung Epithelial Cells ◽  
Second Hand Smoke ◽  
Mesenchymal Transition ◽  
Lung Epithelial ◽  
Tgf Β1

The role of the epithelial–mesenchymal transition (EMT) in lung epithelial cells is increasingly being recognized as a key stage in the development of COPD, fibrosis, and lung cancers, which are all highly associated with cigarette smoking and with exposure to second-hand smoke. Using the exposure of human lung cancer epithelial A549 cells and non-cancerous Beas-2B cells to sidestream cigarette smoke extract (CSE) as a model, we studied the protective effects of adipose-derived stem cell-conditioned medium (ADSC-CM) against CSE-induced cell death and EMT. CSE dose-dependently induced cell death, decreased epithelial markers, and increased the expression of mesenchymal markers. Upstream regulator analysis of differentially expressed genes after CSE exposure revealed similar pathways as those observed in typical EMT induced by TGF-β1. CSE-induced cell death was clearly attenuated by ADSC-CM but not by other control media, such as a pass-through fraction of ADSC-CM or A549-CM. ADSC-CM effectively inhibited CSE-induced EMT and was able to reverse the gradual loss of epithelial marker expression associated with TGF-β1 treatment. CSE or TGF-β1 enhanced the speed of A549 migration by 2- to 3-fold, and ADSC-CM was effective in blocking the cell migration induced by either agent. Future work will build on the results of this in vitro study by defining the molecular mechanisms through which ADSC-CM protects lung epithelial cells from EMT induced by toxicants in second-hand smoke.

scholarly journals Glycyrrhizin suppresses epithelial-mesenchymal transition by inhibiting high-mobility group box1 via the TGF-β1/Smad2/3 pathway in lung epithelial cells

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8514 ◽  
Author(s):  
Yanni Gui ◽  
Jian Sun ◽  
Wenjie You ◽  
Yuanhui Wei ◽  
Han Tian ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Line ◽  
Epithelial Mesenchymal Transition ◽  
High Mobility ◽  
Lung Epithelial Cells ◽  
Epithelial Cell Line ◽  
Mesenchymal Transition ◽  
Lung Epithelial ◽  
Hmgb1 Expression

Background Epithelial-mesenchymal transition (EMT) plays an important role in fibrosis, chronic inflammation, tumor metastasis, etc. Glycyrrhizin, an active component extracted from licorice plant, has been reported to treat a variety of inflammatory reactions through inhibiting high-mobility group box1 (HMGB1), which has been suggested to be a significant mediator in EMT process. However, whether glycyrrhizin affects the EMT process or not remains unclear. Methods Human alveolar epithelial cell line A549 and normal human bronchial epithelial cell line BEAS-2B were treated with extrinsic TGF-β1 to induce EMT. Elisa was used to detect HMGB1 concentrations in cell supernatant. RNA interference and lentivirus infection experiments were performed to investigate the involvement of HMGB1 in EMT process. Cell Counting Kit-8 (CCK-8) was used to detect the viability of A549 and BEAS-2B cells treated with glycyrrhizin. Finally, the effects of glycyrrhizin on EMT changes, as well as the underlying mechanisms, were evaluated via Western blot, immunofluorescence and transwell assays. Results Our results showed that HMGB1 expression was increased by TGF-β1, and knockdown of HMGB1 expression reversed TGF-β1-induced EMT in A549 and BEAS-2B cells. Ectopic HMGB1 expression or TGF-β1 treatment caused a significant increase in HMGB1 release. Notably, we found that glycyrrhizin treatment effectively suppressed TGF-β1-induced EMT process by inhibiting HMGB1. Also, glycyrrhizin significantly inhibited the migration of both A549 and BEAS-2B cells promoted by TGF-β1. Mechanistically, HMGB1 overexpression could activate Smad2/3 signaling in A549 and BEAS-2B cells. Glycyrrhizin significantly blocked the phosphorylation of Smad2/3 stimulated either by TGF-β1 or by ectopic HMGB1 in A549 and BEAS-2B cells. Conclusions HMGB1 is a vital mediator of EMT changes induced by TGF-β1 in lung epithelial cells. Importantly, glycyrrhizin can effectively block Smad2/3 signaling pathway through inhibiting HMGB1, thereby suppressing the EMT progress.

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