Epithelial-mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway
Epithelial-mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway
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DOI：
10.1016/j.toxlet.2014.02.004
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发表时间：
2014-04-21
影响因子：
3.5
通讯作者：
Jia, Guang
中科院分区：
文献类型：
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作者：
Chen, Tian;Nie, Haiyu;Jia, Guang
多壁碳纳米管（MWCNT）是一种典型的具有广泛商业应用的纳米材料。吸入接触MWCNT与肺纤维化和间皮瘤样病变有关，这些病变常见于石棉。在本研究中，我们检测了不同长度的MWCNT对肺纤维化的反应，包括短MWCNT （S-MWCNT，长度= 350-700 nm）和长MWCNT (L-MWCNT，长度= 5-15 μ m)，并研究了MWCNT诱导的肺纤维化过程中是否发生上皮-间质转化（EMT）。C57Bl/6J雄性小鼠气管内灌注S-MWCNT或L-WCNT，每只小鼠单剂量60 μ g，于暴露后7、28和56天评估肺纤维化的进展情况。体内数据显示，只有L-MWCNT显著增加胶原沉积和肺纤维化，约20%的前表面活性剂蛋白c阳性上皮细胞在56天转分化为成纤维细胞，提示EMT的发生。为了了解其机制，我们利用人肺上皮细胞系A549研究tgf - β /p-Smad2信号通路在EMT中的作用。我们的研究结果显示，L-MWCNT下调E-cadherin，上调α -平滑肌肌动蛋白（α - sma）在A549细胞中的表达。综上所述，体内和体外研究均表明，呼吸暴露于MWCNT可通过tgf - β /Smad途径诱导长度依赖性肺纤维化和上皮源性成纤维细胞。2014爱思唯尔爱尔兰有限公司版权所有。
Multi-walled carbon nanotubes (MWCNT) are a typical nanomaterial with a wide spectrum of commercial applications. Inhalation exposure to MWCNT has been linked with lung fibrosis and mesothelioma-like lesions commonly seen with asbestos. In this study, we examined the pulmonary fibrosis response to different length of MWCNT including short MWCNT (S-MWCNT, length = 350-700 nm) and long MWCNT (L-MWCNT, length = 5-15 mu m) and investigated whether the epithelial-mesenchymal transition (EMT) occurred during MWCNT-induced pulmonary fibrosis. C57Bl/6J male mice were intratracheally instilled with S-MWCNT or L-WCNT by a single dose of 60 mu g per mouse, and the progress of pulmonary fibrosis was evaluated at 7, 28 and 56 days post-exposure. The in vivo data showed that only L-MWCNT increased collagen deposition and pulmonary fibrosis significantly, and approximately 20% of pro-surfactant protein-C positive epithelial cells transdifferentiated to fibroblasts at 56 days, suggesting the occurrence of EMT. In order to understand the mechanism, we used human pulmonary epithelial cell line A549 to investigate the role of TGF-beta/p-Smad2 signaling pathway in EMT. Our results showed that L-MWCNT downregulated E-cadherin and upregulated alpha-smooth muscle actin (alpha-SMA) protein expression in A549 cells. Taken together, both in vivo and in vitro study demonstrated that respiratory exposure to MWCNT induced length dependent pulmonary fibrosis and epithelial-derived fibroblasts via TGF-beta/Smad pathway. (C) 2014 Elsevier Ireland Ltd. All rights reserved.