title: Nicotine-induced epithelial-mesenchymal transition via Wnt/β-catenin signaling in human airway epithelial cells.
abstract: Epithelial-mesenchymal transition (EMT) has been proposed to be a mechanism in airway remodeling, which is a characteristic of chronic obstructive pulmonary disease (COPD). Studies have shown that cigarette smoke and nicotine are factors that induce Wnt/β-catenin activation, which is a pathway that has also been implicated in EMT. The main aim of this study was to test whether human bronchial epithelial cells are able to undergo EMT in vitro following nicotine stimulation via the Wnt3a/β-catenin signaling pathway. We show that nicotine activates the Wnt3a signal pathway, which leads to the translocation of β-catenin into the nucleus and activation of β-catenin/Tcf-dependent transcription in the human bronchial epithelial cell (HBEC) line. This accumulation was accompanied by an increase in smooth muscle actin, vimentin, matrix metalloproteinases-9, and type I collagen expression as well as downregulation of E-cadherin, which are typical characteristics of EMT. We also noted that the release of TGF-β(1) from these cells was stimulated by nicotine. Knockdown of Wnt3a with small interfering RNA (siRNA) prevented these effects, implying that β-catenin activation in these responses is Wnt3a dependent. Furthermore, specific knockdown of TGF-β(1) with TGF-β(1) siRNA partially prevented nicotine-induced EMT, suggesting that TGF-β(1) has a role in nicotine-mediated EMT in HBECs. These results suggest that HBECs are able to undergo EMT in vitro upon nicotine stimulation via the Wnt3a/β-catenin signaling pathway.
authors.affiliation: The State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zou
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zou
authors.forename: Zhuxiang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Pixin
authors.initials: P
authors.lastname: Ran
mesh_terms: D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics; D051153:Wnt Proteins / Q000502:physiology*; D060509:Wnt3A Protein / Q000235:genetics; D051176:beta Catenin / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060509:Wnt3A Protein; D051176:beta Catenin; D009538:Nicotine