Cigarette smoke extract alters the cell cycle via the phospholipid transfer protein/transforming growth factor-β1/CyclinD1/CDK4 pathway

被引：13
作者：
Chai, Xue-Min [1 ]
Li, You-Lun [2 ]
Chen, Hong [2 ]
Guo, Shu-Liang [2 ]
Shui, Li-Li [2 ]
Chen, Ya-Juan [2 ]
机构：
[1] Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400016, Peoples R China
[2] Chongqing Med Univ, Affiliated Hosp 1, Resp Dept, Chongqing 400016, Peoples R China
来源：
EUROPEAN JOURNAL OF PHARMACOLOGY | 2016年 / 786卷
关键词：
Phospholipid transfer protein; Cell cycle; Cigarette smoke extract; Transforming growth factor-beta 1; TRANSFER PROTEIN; DNA-DAMAGE; RAT LUNG; II CELLS; SECRETION; APOPTOSIS; DISEASE;
D O I：
10.1016/j.ejphar.2016.05.037
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
This study was aimed to investigate the effect of phospholipid transfer protein (PLTP) on cigarette smoke extract (CSE)-induced alteration of the cell cycle and the possible mechanism. Male Wistar rats and the rat alveolar epithelial cell line (RLE-6TN) were exposed to normal air or different concentrations of CSE. Then PLTP siRNA was transfected into cells and an inhibitor of transforming growth factor-beta 1 (TGF-beta 1) was administered prior to CSE exposure. Histological changes and cell cycle stage were recorded, as were the expression levels of PLTP, TGF-beta 1, CyclinD1 and CDK4. Resulting morphological changes included diffuse interstitial substance incrassation and elevated alveolar rupturing. Flow cytometry analysis revealed an increase in the number of cells in the G1 phase in a time- and dose-related manner. Both PLTP and TGF-beta 1 were up-regulated at protein and mRNA levels, whereas CyclinD1 and CDK4 expression was down-regulated after CSE exposure. Furthermore, PLTP siRNA significantly suppressed CSE-induced TGF-beta 1 expression, resulting in up-regulation of CyclinD1 and CDK4, but the TGF-beta 1 inhibitor was not able to abrogate CSE-induced PLTP over-expression. In conclusion, PLTP may operate upstream of the TGF-beta 1/CyclinD1/CDK4 pathway and may mediate the CSE-induced G1 arrest in RLE-6TN cells. Our work provides some new insight into the relation between PLTP and cell cycle progression. (C) 2016 Elsevier B.V. All rights reserved.
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收藏
页码：85 / 93
页数：9
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