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：68

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

来源：

EXPERIMENTAL LUNG RESEARCH | 2010年 / 36卷 / 01期

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

页码：12 / 24

页数：13

共 36 条

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