The quantification of cell migration is expressed as the mean??SEM

The quantification of cell migration is expressed as the mean??SEM. of fibronectin, E-cadherin, and vimentin through modulating ETS-1 expression. ATN-161, an antagonist of integrin 51, 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. Conclusion O-PMs can induce EMT and fibronectin expression through the activation of transcription factors ETS-1 and NF-B in A549 cells. Norepinephrine 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 Norepinephrine a novel and alternative mechanism for EMT development and pulmonary fibrosis. Keywords: Particulate matters (PMs), EMT, Fibronectin, ETS-1, Pulmonary fibrosis Introduction Fine particulate matter (PM) from Norepinephrine the environment is usually easily inhaled into the respiratory tract, accumulates and penetrates into alveolar cells, and may result in structural damage and functional impairment of the respiratory system [1]. PM can potentially exacerbate pre-existing pulmonary disorders such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, and even cancer [2]. Several mechanisms have been suggested to be involved in the adverse lung effects of PM, including cytotoxicity induced by oxidative stress, DNA damage, mutagenicity, and the activation of inflammatory factors [2]. Our previous study exhibited that PMs increased oxidative stress and inflammatory responses in A549 cells [3]. However, few studies have focused on the formation of fibrosis, the development of epithelial-mesenchymal transition (EMT) and the related mechanisms caused by PMs exposure. This is the most representative event associated with cell fate and requires attention. Fibronectin is an important extracellular matrix (ECM) glycoprotein and plays a vital role in the development of fibrosis [4]. The binding of fibronectin and integrin 51 (the fibronectin receptor) is an important feature of fibrogenesis [5]. High levels of integrin 51 have been found in pulmonary fibrosis of patients with poor prognosis [6]. However, the mechanism associated with PMs-induced pulmonary fibrosis remains unclear. Another important event related to pulmonary fibrosis is usually PM2.5-induced EMT [7]. EMT is the process by which epithelial cells transform into a mesenchymal phenotype and includes the downregulation of epithelial markers, the activation of transcription factors, the upregulation of specific cell surface proteins, the reorganization and expression of cytoskeletal proteins, and the production of ECM-degrading enzymes [8, 9]. Therefore, the molecular mechanisms that regulate the expression of fibronectin and EMT-related proteins may be crucial for the pathogenesis of fibrosis. However, this mechanism has not been studied in detail. Recent studies have highlighted the important role of transcription factors such as p65 NF-B in the pathogenesis of EMT and IL5RA pulmonary fibrosis [10]. Rat type II main alveolar epithelial cells treated with a p65 inhibitor exhibited reduced levels of placental growth factor-induced EMT [11]. The upregulation of p65 expression may be related to chronic inflammation and EMT and further drive the continuous development of pulmonary fibrosis. In addition, the E26 transformation-specific sequence (ETS) family of transcription factors is usually increased in extracellular matrix remodeling, which is an important mechanism Norepinephrine associated with the pathogenesis of idiopathic pulmonary fibrosis [12]. The loss of the ETS domain-containing protein Elk1 prospects to increase integrin 56 expression and exacerbate pulmonary fibrosis in an in vivo fibrosis model [13]. The functions of ETS-1 and p-p65 in the pathogenesis of EMT and pulmonary fibrosis have not been determined. In this study, we aimed to investigate EMT and pulmonary fibrosis induced by PMs exposure in vivo and in vitro. To our knowledge, we showed for the first time that PMs exposure induced EMT and fibrosis in a mouse model. We also showed that the expression of ETS-1 and fibronectin is usually closely related in organic solvent soluble PMs (O-PMs)-treated A549 cells, the lung tissues of PMs-treated Norepinephrine mice, and the lung tissues of patients with pulmonary fibrosis. Results O-PMs induced cell migration and EMT development To determine whether O-PMs exposure plays an important role in promoting EMT, we examined the concentration- and time- dependence of O-PMs-induced A549 cell migration using a wound healing assay. A549 cells were untreated or exposed to different concentrations of O-PMs for 4, 8, and 24?h, and the wounded areas gradually and significantly decreased in a dose-dependent.