title: The pro-proliferative effects of nicotine and its underlying mechanism on rat airway smooth muscle cells.
abstract: Recent studies have shown that nicotine, a major component of cigarette smoke, can stimulate the proliferation of non-neuronal cells. Cigarette smoking can promote a variety of pulmonary and cardiovascular diseases, such as chronic obstructive pulmonary disease (COPD), atherosclerosis, and cancer. A predominant feature of COPD is airway remodeling, which includes increased airway smooth muscle (ASM) mass. The mechanisms underlying ASM remodeling in COPD have not yet been fully elucidated. Here, we show that nicotine induces a profound and time-dependent increase in DNA synthesis in rat airway smooth muscle cells (RASMCs) in vitro. Nicotine also significantly increased the number of RASMCs, which was associated with the increased expression of Cyclin D1, phosphorylation of the retinoblastoma protein (RB) and was dependent on the activation of Akt. The activation of Akt by nicotine occurred within minutes and depended upon the nicotinic acetylcholine receptors (nAchRs). Activated Akt increased the phosphorylation of downstream substrates such as GSK3β. Our data suggest that the binding of nicotine to the nAchRs on RASMCs can regulate cellular proliferation by activating the Akt pathway.
authors.affiliation: Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, 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: Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Zhuxiang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Hu
authors.affiliation: Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zou
authors.affiliation: Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hong
authors.affiliation: Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Changbin
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Dongxing
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Pixin
authors.initials: P
authors.lastname: Ran
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014132:Trachea / Q000166:cytology*
chemical_list: D011978:Receptors, Nicotinic; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D009538:Nicotine; D051057:Proto-Oncogene Proteins c-akt