He Fang, Li Bing, Zhao Zhuxiang, Zhou Yumin, Hu Guoping, Zou Weifeng, Hong Wei, Zou Yimin, Jiang Changbin, Zhao Dongxing, Ran Pixin
Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
The Research Center of Experiment Medicine, Guangzhou Medical University, Guangzhou, Guangdong, China.
PLoS One. 2014 Apr 1;9(4):e93508. doi: 10.1371/journal.pone.0093508. eCollection 2014.
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.
近期研究表明，香烟烟雾的主要成分尼古丁可刺激非神经元细胞增殖。吸烟会引发多种肺部和心血管疾病，如慢性阻塞性肺疾病（COPD）、动脉粥样硬化和癌症。COPD的一个主要特征是气道重塑，其中包括气道平滑肌（ASM）质量增加。COPD中ASM重塑的潜在机制尚未完全阐明。在此，我们表明尼古丁在体外可诱导大鼠气道平滑肌细胞（RASMCs）的DNA合成显著且随时间增加。尼古丁还显著增加了RASMCs的数量，这与细胞周期蛋白D1表达增加、视网膜母细胞瘤蛋白（RB）磷酸化有关，且依赖于Akt的激活。尼古丁对Akt的激活在数分钟内发生，并依赖于烟碱型乙酰胆碱受体（nAchRs）。激活的Akt增加了下游底物如GSK3β的磷酸化。我们的数据表明，尼古丁与RASMCs上的nAchRs结合可通过激活Akt途径调节细胞增殖。
