Tumor necrosis factor-α enhances both epithelial-mesenchymal transition and cell contraction induced in A549 human alveolar epithelial cells by transforming growth factor-β1
Tumor necrosis factor-α enhances both epithelial-mesenchymal transition and cell contraction induced in A549 human alveolar epithelial cells by transforming growth factor-β1
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DOI：
10.3109/01902140903042589
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发表时间：
2010-02-01
影响因子：
1.7
通讯作者：
Nagase, Takahide
中科院分区：
文献类型：
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作者：
Yamauchi, Yasuhiro;Kohyama, Tadashi;Nagase, Takahide
最近，上皮-间充质转化（EMT）已被报道通过增强转化生长因子（TGF）-β 1信号传导促进组织纤维化。肿瘤坏死因子（TNF）-α也与组织纤维化有关。因此，作者研究了TNF-α是否影响TGF-β 1诱导的EMT。培养的肺泡上皮细胞（A549细胞）用TGF-β 1（5 ng/mL）、有/没有TNF-α（10 ng/mL）刺激。TGF-β 1诱导A549细胞发生EMT，E-cadherin丢失，波形蛋白获得。TNF-α与TGF-β 1联合作用可增强EMT，引起形态学改变，而定量聚合酶链反应（PCR）显示E-cadherin mRNA和vimentin mRNA的表达受到抑制。此外，凝胶收缩方法揭示了经历EMT的细胞获得了细胞收缩性，这是间充质细胞的特征。用TGF-β 1刺激诱导细胞收缩，TNF-α也是如此。此外，与TGF-β 1和TNF-α的共刺激增强了细胞收缩。虽然IFN-γ抑制自发性细胞收缩，但它不抑制由TGF-β 1诱导的细胞收缩。总之，TNF-α不仅增强EMT，而且增强TGF-β 1诱导的细胞收缩。EMT可能通过诱导细胞收缩促进组织纤维化。
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.