Cigarette smoke extract induces the epithelial-to-mesenchymal transition via the PLTP/TGF-β 1/Smad2 pathway in RLE-6TN cells

被引：5
作者：
Chen, Hong [1 ]
Wu, Feng-Ping [1 ,2 ]
Yang, Yong-Zhen [2 ]
Yu, Xiu-Ying [1 ]
Zhang, Lu [1 ]
Zhang, Hui [1 ]
Chen, Ya-Juan [1 ]
机构：
[1] Chongqing Med Univ, Affiliated Hosp 1, Dept Resp Med, Chongqing, Peoples R China
[2] Chongqing Med Univ, Neijiang Affiliated Hosp, Dept Resp Med, Neijiang, Sichuan, Peoples R China
来源：
TOXICOLOGY RESEARCH | 2017年 / 6卷 / 02期
关键词：
PHOSPHOLIPID TRANSFER PROTEIN; ROFLUMILAST N-OXIDE; ACUTE LUNG INJURY; MALIGNANT-TRANSFORMATION; 2ND-HAND SMOKE; MESSENGER-RNA; RISK-FACTORS; II CELLS; PLASMA; CANCER;
D O I：
10.1039/c6tx00378h
中图分类号：
R99 [毒物学（毒理学）];
学科分类号：
100405 ;
摘要：
Aim: The role of phospholipid transfer protein (PLTP) in the pathogenesis of the cigarette smoke extract (CSE)-induced epithelial-to-mesenchymal transition (EMT) has not been well described. In this study we investigated the effect of PLTP on the CSE-induced EMT of rat alveolar epithelial cells (RLE-6TN). Methods: The rats were exposed to air and cigarette smoke (CS) for 3 d and then the lungs were sectioned and examined using immunohistochemistry techniques. RLE-6TN cells were treated with different concentrations of CSE. PLTP siRNA was transfected into cells or SB431542 - an inhibitor of the transforming growth factor-beta 1 (TGF-beta 1) type I receptor - was administered prior to CSE exposure. The expression of EMT markers and PLTP was detected by qRT-PCR. The levels of PLTP, TGF-beta 1, p-Smad2, Smad2, and EMT proteins were analyzed by western blotting. Results: Lung injury and EMT were accompanied by up-regulation of PLTP and TGF-beta 1 in the CS-exposed rat model. EMT was induced by CSE in vitro, and the expression of PLTP, TGF-beta 1, and p-Smad2 was significantly increased after exposure to CSE (P < 0.05). Moreover, knockdown of PLTP and blocking of the TGF-beta 1/Smad2 pathway restrained the CSE-induced activation of the TGF-beta 1/Smad2 pathway and partly inhibited EMT by reversing E-cadherin expression and retarding the induction of N-cadherin and vimentin. In contrast, SB431542 had no effect on the expression of PLTP, while it ameliorated CSE-induced EMT. Conclusion: PLTP promotes the CSE-induced EMT process, in which the TGF-beta 1/Smad2 pathway is activated.
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页码：215 / 222
页数：8
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