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.
['Chai|Xue-Min|XM|', 'Li|You-Lun|YL|', 'Chen|Hong|H|', 'Guo|Shu-Liang|SL|', 'Shui|Li-Li|LL|', 'Chen|Ya-Juan|YJ|']
D000818:Animals D019938:Cyclin D1 D051358:Cyclin-Dependent Kinase 4 D059585:G1 Phase Cell Cycle Checkpoints D008168:Lung D008297:Male D049294:Phospholipid Transfer Proteins D051381:Rats D017208:Rats, Wistar D015398:Signal Transduction D012906:Smoke D014026:Tobacco D053773:Transforming Growth Factor beta1
Cigarette smoke extract Cell cycle Phospholipid transfer protein Transforming growth factor-β1