Tumor necrosis factor-α enhances both epithelial-mesenchymal transition and cell contraction induced in A549 human alveolar epithelial cells by transforming growth factor-β1

被引:67
|
作者
Yamauchi, Yasuhiro [1 ]
Kohyama, Tadashi [1 ]
Takizawa, Hajime [2 ]
Kamitani, Sumiko [1 ]
Desaki, Masashi [1 ]
Takami, Kazutaka [1 ]
Kawasaki, Shin [1 ]
Kato, Jun [1 ]
Nagase, Takahide [1 ]
机构
[1] Univ Tokyo, Dept Resp Med, Tokyo, Japan
[2] Teikyo Univ, Dept Internal Med 4, Tokyo 173, Japan
关键词
alveolar epithelial cell; cell contractility; epithelial mesenchymal transition; pulmonary fibrosis; TGF-beta; 1; TNF-alpha; GROWTH-FACTOR-BETA; FIBROBLAST-MEDIATED CONTRACTION; IDIOPATHIC PULMONARY-FIBROSIS; TRANSCRIPTION FACTOR SNAIL; INTERFERON-GAMMA; GENE-EXPRESSION; GEL CONTRACTION; COLLAGEN GELS; TGF-BETA-1; GLUCOCORTICOIDS;
D O I
10.3109/01902140903042589
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Recently, epithelial-mesenchymal transition (EMT) has been reported to contribute to tissue fibrosis through enhanced transforming growth factor (TGF)-beta 1 signaling. Tumor necrosis factor (TNF)-alpha has also been implicated in tissue fibrosis. Therefore, the authors investigated whether TNF-alpha affected TGF-beta 1-induced EMT. Cultured alveolar epithelial cells (A549 cells) were stimulated with TGF-beta 1 (5 ng/mL), with/without TNF-alpha (10 ng/mL). TGF-beta 1 induced EMT of A549 cells, with loss of E-cadherin and acquisition of vimentin. Combination of TNF-alpha with TGF-beta 1 enhanced EMT, causing morphological changes, while quantitative polymerase chain reaction (PCR) showed suppression of E-cadherin mRNA and expression of vimentin mRNA. In addition, the gel contraction method revealed that cells that had undergone EMT acquired cell contractility, which is a feature of mesenchymal cells. Stimulation with TGF-beta 1 induced cell contraction, as did TNF-alpha. Moreover, costimulation with TGF-beta 1 and TNF-alpha enhanced the cell contraction. Although IFN-gamma suppressed spontaneous cell contraction, it did not suppress cell contraction, which was induced by TGF-beta 1. In conclusion, TNF-alpha enhances not only EMT but also cell contraction induced by TGF-beta 1. EMT might contribute to tissue fibrosis through induction of cell contraction.
引用
收藏
页码:12 / 24
页数:13
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