title: Nicotine reduces the levels of surfactant proteins A and D via Wnt/β-catenin and PKC signaling in human airway epithelial cells.
abstract: A deficiency of surfactant proteins A and D has been proposed as a mechanism in airway remodeling, which is one characteristic of chronic obstructive pulmonary disease (COPD). We recently showed that in vitro nicotine exposure induces Wnt3a/β-catenin activation, which is a pathway that has also been implicated in altering levels of SP-A and SP-D. Nicotine induced activation of protein kinase C(PKC), and the involvement of PKC in mediating Wnt signaling has been demonstrated previously. The main aim of this study was to investigate whether human bronchial epithelial cells reduce levels of SP-A and SP-D in vitro following nicotine stimulation via the Wnt3a/β-catenin and PKC signaling pathway. We showed that nicotine activated the Wnt3a/β-catenin and PKC signaling pathway, and this activation was accompanied by a decrease in SP-A and SP-D expression. Knockdown of Wnt3a with small interfering RNA (siRNA) prevented translocation of β-catenin into the nucleus and reduction levels of SP-A and SP-D. Furthermore, a PKC inhibitor partially prevented these effects,which suggests in HBECs, Wnt3a/β-catenin and PKC pathways interact during nicotine-reduced levels of SP-A and SP-D. These results suggest that HBECs reduce the levels of surfactant proteins A and D in vitro via the Wnt3a/β-catenin and PKC signaling pathway upon nicotine stimulation.
authors.affiliation: Guangzhou Chest Hospital, The State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zou
authors.affiliation: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Liu
authors.affiliation: Guangzhou Chest Hospital, The State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong, China.
authors.forename: Jinxing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Guangzhou Chest Hospital, The State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sheng
authors.affiliation: The Research Center of Experiment Medicine, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Fang
authors.initials: F
authors.lastname: He
authors.affiliation: The Research Center of Experiment Medicine, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China. Electronic address: pxran@vip.163.com.
authors.forename: Pixin
authors.initials: P
authors.lastname: Ran
mesh_terms: D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009281:Naphthalenes / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D009281:Naphthalenes; D018722:Nicotinic Agonists; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D034741:RNA, Small Interfering; D009538:Nicotine; D011493:Protein Kinase C; C058819:calphostin C
keywords: Bronchial epithelial cell; Nicotine; SP-A; SP-D