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Particulate matters increase epithelial-mesenchymal transition and lung fibrosis through the ETS-1/NF-κB-dependent pathway in lung epithelial cells.
Particle and Fibre Toxicology ( IF 10 ) Pub Date : 2020-08-14 , DOI: 10.1186/s12989-020-00373-z
Yu-Chen Chen , Tzu-Yi Chuang , Chen-Wei Liu , Chi-Wei Liu , Tzu-Lin Lee , Tsai-Chun Lai , Yuh-Lien Chen

Particulate matters (PMs) in ambient air pollution are closely related to the incidence of respiratory diseases and decreased lung function. Our previous report demonstrated that PMs-induced oxidative stress increased the expression of proinflammatory intracellular adhesion molecule-1 (ICAM-1) through the IL-6/AKT/STAT3/NF-κB pathway in A549 cells. However, the role of O-PMs in epithelial-mesenchymal transition (EMT) development and pulmonary fibrosis and the related mechanisms have not been determined. The aim of this study was to investigate the effects of O-PMs on the pathogenesis of EMT and pulmonary fibrosis as well as the expression of ETS-1 and NF-κB p65, in vitro and in vivo. O-PMs treatment induced EMT development, fibronectin expression, and cell migration. O-PMs affected the expression of the EMT-related transcription factors NF-κB p65 and ETS-1. Interference with NF-κB p65 significantly decreased O-PMs-induced fibronectin expression. In addition, O-PMs affected the expression of fibronectin, E-cadherin, and vimentin through modulating ETS-1 expression. ATN-161, an antagonist of integrin α5β1, decreased the expression of fibronectin and ETS-1 and EMT development. EMT development and the expression of fibronectin and ETS-1 were increased in the lung tissue of mice after exposure to PMs for 7 and 14 days. There was a significant correlation between fibronectin and ETS-1 expression in human pulmonary fibrosis tissue. O-PMs can induce EMT and fibronectin expression through the activation of transcription factors ETS-1 and NF-κB in A549 cells. PMs can induce EMT development and the expression of fibronectin and ETS-1 in mouse lung tissues. These findings suggest that the ETS-1 pathway could be a novel and alternative mechanism for EMT development and pulmonary fibrosis.

中文翻译:

颗粒物质通过肺上皮细胞中的ETS-1 /NF-κB依赖性途径增加上皮-间质转化和肺纤维化。

周围空气污染中的颗粒物(PMs)与呼吸系统疾病的发生和肺功能下降密切相关。我们以前的报告表明,PMs诱导的氧化应激通过A549细胞中的IL-6 / AKT / STAT3 /NF-κB途径增加了促炎性细胞内粘附分子1(ICAM-1)的表达。但是,O-PM在上皮-间质转化(EMT)发育和肺纤维化中的作用及其相关机制尚未确定。这项研究的目的是在体外和体内研究O-PMs对EMT和肺纤维化的发病机制以及ETS-1和NF-κBp65表达的影响。O-PMs处理可诱导EMT发育,纤连蛋白表达和细胞迁移。O-PM影响EMT相关转录因子NF-κBp65和ETS-1的表达。干扰NF-κBp65会显着降低O-PMs诱导的纤连蛋白表达。此外,O-PM通过调节ETS-1表达来影响纤连蛋白,E-钙粘着蛋白和波形蛋白的表达。整合素α5β1的拮抗剂ATN-161降低了纤连蛋白和ETS-1的表达以及EMT的发育。暴露于PM 7天和14天后,小鼠肺组织中EMT的发育以及纤连蛋白和ETS-1的表达增加。在人肺纤维化组织中纤连蛋白和ETS-1表达之间存在显着相关性。O-PMs可以通过激活A549细胞中的转录因子ETS-1和NF-κB来诱导EMT和纤连蛋白的表达。PMs可以诱导EMT的发展以及小鼠肺组织中纤连蛋白和ETS-1的表达。这些发现表明,ETS-1途径可能是EMT发展和肺纤维化的一种新颖的替代机制。
更新日期:2020-08-14
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