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.

The lack of attachment of transformed embryonic lung epithelial cells to collagen I is corrected by fibronectin and FXIII

1986 ◽  
Vol 86 (1) ◽  
pp. 95-107
Author(s):  
M. Paye ◽  
C.M. Lapiere
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Line ◽  
Lung Epithelial Cells ◽  
Collagen I ◽  
Epithelial Cell Line ◽  
Embryonic Lung ◽  
Lung Epithelial ◽  
Minimal Concentration ◽  
Pulmonary Epithelial Cell

PER cells, a transformed pulmonary epithelial cell line that adhered to a large extent to a fibronectin substratum, were found to be attachment-deficient to collagen I. Although fibronectin can bind to collagen I monomers and polymers, the addition of exogenous fibronectin in the attachment medium induced the adhesion of these cells to collagen I polymers but not to monomers. By adding the transglutaminase of blood coagulation, FXIII, in the presence of fibronectin, the attachment of PER cells to collagen I monomers could be recovered while the minimal concentration of fibronectin needed to promote their adhesion to polymers was lowered. These studies indicate that FXIII enhances the fibronectin-mediated attachment of PER cells to collagen I.

scholarly journals Neutrophil extracellular traps induce the epithelial-mesenchymal transition: implications in post-COVID-19 fibrosis

2020 ◽  
Author(s):  
Laura Pandolfi ◽  
Sara Bozzini ◽  
Vanessa Frangipane ◽  
Elena Percivalle ◽  
Ada De Luigi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Tissue Injury ◽  
Neutrophil Extracellular Traps ◽  
Lung Epithelial Cells ◽  
Epithelial Cell Line ◽  
High Concentration ◽  
Mesenchymal Transition ◽  
Extracellular Traps ◽  
Lung Epithelial

AbstractThe release of neutrophil extracellular traps (NETs), a process termed NETosis, avoids pathogen spread but may cause tissue injury. NETs have been found in severe COVID-19 patients, but their role in disease development is still unknown. The aim of this study is to assess the capacity of NETs to drive epithelial-mesenchymal transition (EMT) of lung epithelial cells and to analyze the involvement of NETs in COVID-19.Neutrophils activated with PMA (PMA-Neu), a stimulus known to induce NETs formation, induce both EMT and cell death in the lung epithelial cell line, A549. Notably, NETs isolated from PMA-Neu induce EMT without cell damage. Bronchoalveolar lavage fluid of severe COVID-19 patients showed high concentration of NETs. Thus, we tested in an in vitro alveolar model the hypothesis that virus-induced NET may drive EMT. Co-culturing A549 at air-liquid interface with alveolar macrophages, neutrophils and SARS-CoV2, we demonstrated a significant induction of the EMT in A549 together with high concentration of NETs, IL8 and IL1β, best-known inducers of NETosis. Lung tissues of COVID-19 deceased patients showed that epithelial cells are characterized by increased mesenchymal markers. These results show for the first time that NETosis plays a major role in triggering lung fibrosis in COVID-19 patients.

scholarly journals The Severe Acute Respiratory Syndrome Coronavirus 3a Protein Up-Regulates Expression of Fibrinogen in Lung Epithelial Cells

2005 ◽  
Vol 79 (15) ◽  
pp. 10083-10087 ◽  
Author(s):  
Yee-Joo Tan ◽  
Puay-Yoke Tham ◽  
Daphne Z. L. Chan ◽  
Chih-Fong Chou ◽  
Shuo Shen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Cell Line ◽  
Pulmonary Complications ◽  
Lung Epithelial Cells ◽  
Epithelial Cell Line ◽  
Mrna Levels ◽  
Lung Epithelial

ABSTRACT Here we analyzed the gene expression profile of cells that stably express the severe acute respiratory syndrome coronavirus (SARS-CoV) 3a protein to determine its effects on host functions. A lung epithelial cell-line, A549, was chosen for this study because the lung is the primary organ infected by SARS-CoV and fatalities resulted mainly from pulmonary complications. Our results showed that the expression of 3a up-regulates the mRNA levels of all three subunits, Aα, Bβ, and γ, of fibrinogen. Consequently, the intracellular levels as well as the secretion of fibrinogen were increased. We also observed increased fibrinogen levels in SARS-CoV-infected Vero E6 cells.

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