Cigarette smoke extract induces activation of beta-catenin/TCF signaling through inhibiting GSK3beta in human alveolar epithelial cell line.
Cigarette smoke is known to have various injurious and cytotoxic effects on alveolar epithelial cells. However, the mechanism about the effects caused by cigarette smoke on alveolar epithelial cells remains unclear. In the present study, we first validated that cigarette smoke extract (CSE) impaired the viability of alveolar epithelial cells (A549 cells) and resulted in some morphological changes. Next, we found that glycogen synthase kinase 3beta (GSK3beta) was highly expressed in A549 cells, and CSE significantly inhibited GSK3beta by reducing GSK3beta expression and increasing inactive phosphorylated GSK3beta. It was also observed that CSE promoted beta-catenin accumulation and nuclear translocation, and further activated beta-catenin/TCF signaling. Finally, we demonstrated that GSK3beta over-expression promoted the degradation of beta-catenin and abolished beta-catenin/TCF transcriptional activity that was induced by CSE in alveolar epithelial cells. These results suggest that CSE induces the activation of beta-catenin/TCF signaling through inhibiting GSK3beta, implying a possible mechanism responsible for the injurious and cytotoxic effects on alveolar epithelial cell caused by cigarette smoke.
Department of Pathology, Shanghai First People's Hospital, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200080, PR China.
Dan
D
Tian
Min
M
Zhu
Jiansha
J
Li
Yan
Y
Ma
Renliang
R
Wu
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000009:adverse effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008175:Lung Neoplasms; D009538:Nicotine / Q000032:analysis; D010947:Plants, Toxic / Q000737:chemistry; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects*; D012906:Smoke / Q000009:adverse effects* / Q000032:analysis; D013638:Tars / Q000032:analysis; D014026:Nicotiana / Q000737:chemistry*; D051176:beta Catenin / Q000378:metabolism*
D004791:Enzyme Inhibitors; D012906:Smoke; D013638:Tars; D051176:beta Catenin; C024746:tobacco tar; D009538:Nicotine; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3