Cigarette smoke extract alters the cell cycle via the phospholipid transfer protein/transforming growth factor-β1/CyclinD1/CDK4 pathway.
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-β1 (TGF-β1) was administered prior to CSE exposure. Histological changes and cell cycle stage were recorded, as were the expression levels of PLTP, TGF-β1, 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-β1 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-β1 expression, resulting in up-regulation of CyclinD1 and CDK4, but the TGF-β1 inhibitor was not able to abrogate CSE-induced PLTP over-expression. In conclusion, PLTP may operate upstream of the TGF-β1/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.
The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: 695020596@qq.com.
Xue-Min
XM
Chai
Respiratory Department, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: liyoulun83@163.com.
You-Lun
YL
Li
Respiratory Department, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: hopehong2003@126.com.
Hong
H
Chen
Respiratory Department, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: GUOSL999@sina.com.
Shu-Liang
SL
Guo
Respiratory Department, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: 476396186@qq.com.
Li-Li
LL
Shui
Respiratory Department, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: yajuanchencqmu@sina.com.
Ya-Juan
YJ
Chen
D000818:Animals; D019938:Cyclin D1 / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008297:Male; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D049294:Phospholipid Transfer Proteins; D012906:Smoke; D053773:Transforming Growth Factor beta1; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4
Cell cycle; Cigarette smoke extract; Phospholipid transfer protein; Transforming growth factor-β1