1. Tumor necrosis factor-α enhances both epithelial-mesenchymal transition and cell contraction induced in A549 human alveolar epithelial cells by transforming growth factor-β1.
- Author
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Yamauchi, Yasuhiro, Kohyama, Tadashi, Takizawa, Hajime, Kamitani, Sumiko, Desaki, Masashi, Takami, Kazutaka, Kawasaki, Shin, Kato, Jun, and Nagase, Takahide
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TUMOR necrosis factors , *CELL contraction , *ALVEOLAR nerve , *EPITHELIAL cells , *POLYMERASE chain reaction , *MESSENGER RNA , *FIBROSIS - Abstract
Recently, epithelial-mesenchymal transition (EMT) has been reported to contribute to tissue fibrosis through enhanced transforming growth factor (TGF)-β1 signaling. Tumor necrosis factor (TNF)-α has also been implicated in tissue fibrosis. Therefore, the authors investigated whether TNF-α affected TGF-β1-induced EMT. Cultured alveolar epithelial cells (A549 cells) were stimulated with TGF-β1 (5 ng/mL), with/without TNF-α (10 ng/mL). TGF-β1 induced EMT of A549 cells, with loss of E-cadherin and acquisition of vimentin. Combination of TNF-α with TGF-β1 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-β1 induced cell contraction, as did TNF-α. Moreover, costimulation with TGF-β1 and TNF-α enhanced the cell contraction. Although IFN-γ suppressed spontaneous cell contraction, it did not suppress cell contraction, which was induced by TGF-β1. In conclusion, TNF-α enhances not only EMT but also cell contraction induced by TGF-β1. EMT might contribute to tissue fibrosis through induction of cell contraction. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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