Effects of Chrysotile Exposure in Human Bronchial Epithelial Cells: Insights into the Pathogenic Mechanisms of Asbestos-Related Diseases.
Effects of Chrysotile Exposure in Human Bronchial Epithelial Cells: Insights into the Pathogenic Mechanisms of Asbestos-Related Diseases.
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DOI：
10.1289/ehp.1409627
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发表时间：
2016-06
影响因子：
10.4
通讯作者：
Aldieri E
中科院分区：
文献类型：
--
作者：
Gulino GR;Polimeni M;Prato M;Gazzano E;Kopecka J;Colombatto S;Ghigo D;Aldieri E
温石棉占全世界使用的石棉的90%以上，接触与石棉沉滞症（石棉相关的纤维化）和其他恶性肿瘤有关;然而，所涉及的分子机制尚未完全了解。这些恶性肿瘤的常见致病机制由上皮-间充质转化（EMT）表示，通过EMT，上皮细胞经历形态学转化以呈现间充质表型。在目前的工作中，我们提出，温石棉诱导EMT的机制，涉及的信号转导通路的转化生长因子β（TGF-β）。我们研究了温石棉在诱导EMT中的作用，以阐明参与这一事件的分子机制。用1 μg/cm ~ 2温石棉孵育人支气管上皮细胞（BEAS-2B）≤ 72小时，观察了EMT的几种标志物。用TGF-β、糖原合成酶激酶-3 β（GSK-3β）和Akt的特异性抑制剂进行实验以证实它们参与石棉诱导的EMT。实时聚合酶链反应（PCR），蛋白质印迹法，明胶酶谱法进行检测这些标志物的mRNA和蛋白质水平的变化。温石棉激活TGF-β介导的信号通路，涉及Akt、GSK-3β和SNAIL-1的作用。BEAS-2B细胞中该途径的激活与上皮标志物（E-钙粘蛋白和β-连环蛋白）的减少和间充质标志物（α-平滑肌肌动蛋白、波形蛋白、金属蛋白酶和纤连蛋白）的增加相关。我们的研究结果表明，温石棉诱导EMT，石棉相关疾病的常见事件，至少部分通过引发TGF-β介导的Akt/GSK-3β/SNAIL-1途径。Gulino GR，Polimeni M，普拉托M，Gazzano E，Kopecka J，Colombatto S，Ghigo D，Aldieri E. 2016.温石棉暴露对人支气管上皮细胞的影响：石棉相关疾病致病机制的研究。环境健康展望124：776-784; http://dx.doi.org/10.1289/ehp.1409627
Chrysotile asbestos accounts for > 90% of the asbestos used worldwide, and exposure is associated with asbestosis (asbestos-related fibrosis) and other malignancies; however, the molecular mechanisms involved are not fully understood. A common pathogenic mechanism for these malignancies is represented by epithelial–mesenchymal transition (EMT), through which epithelial cells undergo a morphological transformation to assume a mesenchymal phenotype. In the present work, we propose that chrysotile asbestos induces EMT through a mechanism involving a signaling pathway mediated by tranforming growth factor beta (TGF-β). We investigated the role of chrysotile asbestos in inducing EMT in order to elucidate the molecular mechanisms involved in this event. Human bronchial epithelial cells (BEAS-2B) were incubated with 1 μg/cm2 chrysotile asbestos for ≤ 72 hr, and several markers of EMT were investigated. Experiments with specific inhibitors for TGF-β, glycogen synthase kinase–3β (GSK-3β), and Akt were performed to confirm their involvement in asbestos-induced EMT. Real-time polymerase chain reaction (PCR), Western blotting, and gelatin zymography were performed to detect mRNA and protein level changes for these markers. Chrysotile asbestos activated a TGF-β–mediated signaling pathway, implicating the contributions of Akt, GSK-3β, and SNAIL-1. The activation of this pathway in BEAS-2B cells was associated with a decrease in epithelial markers (E-cadherin and β-catenin) and an increase in mesenchymal markers (α-smooth muscle actin, vimentin, metalloproteinases, and fibronectin). Our findings suggest that chrysotile asbestos induces EMT, a common event in asbestos-related diseases, at least in part by eliciting the TGF-β–mediated Akt/GSK-3β/SNAIL-1 pathway. Gulino GR, Polimeni M, Prato M, Gazzano E, Kopecka J, Colombatto S, Ghigo D, Aldieri E. 2016. Effects of chrysotile exposure in human bronchial epithelial cells: insights into the pathogenic mechanisms of asbestos-related diseases. Environ Health Perspect 124:776–784; http://dx.doi.org/10.1289/ehp.1409627