scholarly journals Effect of CDH1 gene methylation on transforming growth factor (TGF-β)-induced epithelial-mesenchymal transition in alveolar epithelial cell line A549

2014 ◽  
Vol 13 (4) ◽  
pp. 8568-8576 ◽  
Author(s):  
Y.Y. Liu ◽  
J.Y. Han ◽  
S.C. Lin ◽  
Z.Y. Liu ◽  
W.T. Jiang
Keyword(s):  
Growth Factor ◽  
Epithelial Cell ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Alveolar Epithelial Cell ◽  
Epithelial Cell Line ◽  
Gene Methylation ◽  
Cdh1 Gene ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial

scholarly journals GED-0507 attenuates lung fibrosis by counteracting myofibroblast transdifferentiation in vivo and in vitro

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257281
Author(s):  
Silvia Speca ◽  
Caroline Dubuquoy ◽  
Christel Rousseaux ◽  
Philippe Chavatte ◽  
Pierre Desreumaux ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Alveolar Epithelial Cell ◽  
Lung Fibroblasts ◽  
Epithelial Cell Line ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Ppar Γ

The development of more effective, better tolerated drug treatments for progressive pulmonary fibrosis (of which idiopathic pulmonary fibrosis is the most common and severe form) is a research priority. The peroxisome proliferator-activated receptor gamma (PPAR-γ) is a key regulator of inflammation and fibrosis and therefore represents a potential therapeutic target. However, the use of synthetic PPAR-γ agonists may be limited by their potentially severe adverse effects. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, we have demonstrated that the non-racemic selective PPAR-γ modulator GED-0507 is able to reduce body weight loss, ameliorate clinical and histological features of pulmonary fibrosis, and increase survival rate without any safety concerns. Here, we focused on the biomolecular effects of GED-0507 on various inflammatory/fibrotic pathways. We demonstrated that preventive and therapeutic administration of GED-0507 reduced the BLM-induced mRNA expression of several markers of fibrosis, including transforming growth factor (TGF)-β, alpha-smooth muscle actin, collagen and fibronectin as well as epithelial-to-mesenchymal transition (EMT) and expression of mucin 5B. The beneficial effect of GED-0507 on pulmonary fibrosis was confirmed in vitro by its ability to control TGFβ-induced myofibroblast activation in the A549 human alveolar epithelial cell line, the MRC-5 lung fibroblast line, and primary human lung fibroblasts. Compared with the US Food and Drug Administration-approved antifibrotic drugs pirfenidone and nintedanib, GED-0507 displayed greater antifibrotic activity by controlling alveolar epithelial cell dysfunction, EMT, and extracellular matrix remodeling. In conclusion, GED-0507 demonstrated potent antifibrotic properties and might be a promising drug candidate for the treatment of pulmonary fibrosis.

Methotrexate-Induced Epithelial–Mesenchymal Transition in the Alveolar Epithelial Cell Line A549

Lung ◽  
2016 ◽  
Vol 194 (6) ◽  
pp. 923-930 ◽  
Author(s):  
Masashi Kawami ◽  
Rika Harabayashi ◽  
Mioka Miyamoto ◽  
Risako Harada ◽  
Ryoko Yumoto ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Line ◽  
Epithelial Mesenchymal Transition ◽  
Alveolar Epithelial Cell ◽  
Epithelial Cell Line ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial

Transforming growth factor-alpha enhances alveolar epithelial cell repair in a new in vitro model

1994 ◽  
Vol 267 (6) ◽  
pp. L728-L738 ◽  
Author(s):  
F. Kheradmand ◽  
H. G. Folkesson ◽  
L. Shum ◽  
R. Derynk ◽  
R. Pytela ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cell ◽  
Wound Repair ◽  
Wound Closure ◽  
Transforming Growth Factor ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial ◽  
Factor Alpha ◽  
Vitro Model

Alveolar epithelial type II cells are essential for regenerating an intact alveolar barrier after destruction of type I cells in vivo. The first objective of these experimental studies was to develop an in vitro model to quantify alveolar epithelial cell wound repair. The second objective was to investigate mechanisms of alveolar epithelial cell wound healing by studying the effects of serum and transforming growth factor-alpha (TGF-alpha) on wound closure. Primary cultures of rat alveolar type II cells were prepared by standard methods and grown to form confluent monolayers in 48 h. Then a wound was made by denuding an area (mean initial area of 2.1 +/- 0.6 mm2) of the monolayer. Re-epithelialization of the denuded area over time in the presence or absence of serum was measured using quantitative measurements from time-lapse video microscopy. The half time of wound healing was significantly enhanced in the presence of serum compared with serum-free conditions (2.4 +/- 0.2 vs. 17.4 +/- 0.8 h, P < 0.001). We then tested the hypothesis that TGF-alpha is an important growth factor for stimulating wound repair of alveolar epithelial cells. Exogenous addition of TGF-alpha in serum-free medium resulted in a significantly more rapid wound closure, and, furthermore, the addition of a monoclonal antibody to TGF-alpha in the presence of serum significantly decreased fourfold the rate of wound closure. Measurement of internuclear cell distance confirmed that both cell motility and cell spreading were responsible for closure of the wound. These data demonstrate that 1) the mechanisms of alveolar cell repair can be studied in vitro and that 2) TGF-alpha is a potent growth factor that enhances in vitro alveolar epithelial cell wound closure.

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