CTNNAL1 inhibits ozone-induced epithelial-mesenchymal transition in human bronchial epithelial cells
CTNNAL1 inhibits ozone-induced epithelial-mesenchymal transition in human bronchial epithelial cells
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CTNNAL1抑制臭氧诱导的人支气管上皮细胞上皮间质转化
DOI：
10.1113/ep086839
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发表时间：
2018-08-01
影响因子：
2.7
通讯作者：
Xiang, Yang
中科院分区：
文献类型：
--
作者：
Tan, Meiling;Liu, Caixia;Xiang, Yang
上皮-间质转化（EMT）是上皮和间质修复过程中的一个重要事件，是气道重塑的一个可能机制。我们前期的研究表明，哮喘模型支气管上皮细胞中catenin alpha-like 1（CTNNAL 1）表达下调，在气道上皮损伤修复中起重要作用。本研究的目的是研究CTNNAL 1对气道EMT的影响。通过稳定转染诱导CTNNAL 1在人支气管上皮细胞中的过表达或沉默。用有效的siRNA载体在原代小鼠气道上皮细胞中沉默CTNNAL 1。在第（-1）天30分钟时用臭氧胁迫细胞4天以诱导EMT。EMT的功能，共培养的肺成纤维细胞的功能的变化，在转录抑制因子蜗牛/蛞蝓和Twist 1/Twist 2的表达的变化和转化生长因子β 1（TGF-β 1）的分泌的变化进行了测定在不同的细胞系与或没有臭氧暴露。臭氧暴露和CTNNAL 1沉默均诱导气道上皮细胞的EMT特征。肺成纤维细胞的功能变化增加后，与（臭氧应激）CTNNAL 1沉默的细胞共培养。Snail和Twist 1表达增加，TGF-β 1水平增强。相反，CTNNAL 1过表达逆转EMT特征，抑制Twist 1的mRNA水平，并减少TGF-β 1的分泌，无论是单独还是与臭氧暴露相结合。我们的研究结果表明，臭氧暴露诱导气道EMT和CTNNAL 1抑制臭氧诱导的气道EMT。CTNAL 1可能通过抑制Twist 1 mRNA的表达和降低TGF-β 1的水平在气道EMT中发挥作用。
Epithelial-mesenchymal transition (EMT), a crucial event occurring during epithelial and mesenchymal repair, was reported to be a possible mechanism for airway remodelling. Our previous work showed that the expression of catenin alpha-like 1 (CTNNAL1) was down-regulated in the bronchial epithelial cells of asthmatic models and played a vital role in airway epithelial wound repair. The aim of this study was to investigate the effect of CTNNAL1 on airway EMT. Overexpression or silencing of CTNNAL1 in human bronchial epithelial cells was induced by stable transfection. CTNNAL1 was silenced in primary mouse airway epithelial cells with an effective siRNA vector. Cells were stressed by ozone for 4 days at 30 min day(-1) to induce EMT. EMT features, changes in the function of co-cultured lung fibroblasts, changes in the expression of the transcriptional repressors Snail/Slug and Twist1/Twist2 and changes in the secretion of transforming growth factor beta 1 (TGF-beta 1) were assayed in different cell lines with or without ozone exposure. Both ozone exposure and silencing of CTNNAL1 induced EMT features in airway epithelial cells. Functional changes in lung fibroblasts increased after co-culture with (ozone-stressed) CTNNAL1-silenced cells. Snail and Twist1 expression increased, and the level of TGF-beta 1 was enhanced. Conversely, CTNNAL1 overexpression reversed EMT features, repressed mRNA levels of Twist1 and reduced the secretion of TGF-beta 1, both alone and in combination with ozone exposure. Our results indicate that ozone exposure induces airway EMT and that CTNNAL1 inhibits ozone-induced airway EMT. CTNNAL1 may play a role in airway EMT by repressing the expression of Twist1 mRNA and reducing the level of TGF-beta 1.