Change of extracellular signal-regulated kinase expression in pulmonary arteries from smokers with and without chronic obstructive pulmonary disease
Change of extracellular signal-regulated kinase expression in pulmonary arteries from smokers with and without chronic obstructive pulmonary disease
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患有和不患有慢性阻塞性肺疾病的吸烟者肺动脉中细胞外信号调节激酶表达的变化
DOI：
10.3109/01902148.2013.788234
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发表时间：
2013-05-01
影响因子：
1.7
通讯作者：
Xu, Yong-Jian
中科院分区：
文献类型：
--
作者：
Liu, Kui;Liu, Xian-Sheng;Xu, Yong-Jian
背景：吸烟可能通过导致肺动脉血管重构（包括肺动脉平滑肌细胞（PASMC）增殖）导致慢性阻塞性肺疾病（COPD）患者肺动脉高压。然而，这一过程背后的分子机制仍然知之甚少。目的：本研究的目的是探讨细胞外信号调节激酶（ERK）在肺功能正常的吸烟者和轻中度COPD吸烟者肺动脉中的作用。方法：选取14例肺功能正常的非吸烟者、18例肺功能正常的吸烟者和16例轻中度COPD吸烟者的肺外周组织。苏木精-伊红（HE）染色观察肺动脉形态变化。原代培养的人肺动脉平滑肌细胞（HPASMCs）暴露于香烟烟雾提取物（CSE）。细胞计数法和甲基噻唑四氮唑法测定细胞增殖。western blotting分析蛋白表达。结果：形态计量学分析显示，吸烟组和COPD组肺血管壁厚度均显著大于非吸烟组（P < 0.01）。与不吸烟组相比，吸烟组和COPD组ERK蛋白水平明显升高（P < 0.01）。5% CSE在蛋白水平上显著提高了HPASMCs中ERK的表达（P < 0.01），显著促进了HPASMCs的增殖（P < 0.01）。结论：ERK表达升高可能参与了伴有或不伴有COPD的吸烟者PASMCs异常增殖的发病机制。
ABSTRACT Background: Cigarette smoking may contribute to pulmonary hypertension in chronic obstructive pulmonary disease (COPD) by resulting in pulmonary vascular remodeling that involves pulmonary artery smooth muscle cell (PASMC) proliferation. However, the molecular mechanism underlying this process remains poorly understood. Objectives: The purpose of this study was to investigate the role of extracellular signal-regulated kinase (ERK) in pulmonary arteries from smokers with normal lung function and smokers with mild to moderate COPD. Methods: The peripheral lung tissues were obtained from 14 nonsmokers with normal lung function, 18 smokers with normal lung function, and 16 smokers with mild to moderate COPD. The morphological changes of pulmonary arteries were observed by hematoxylin-eosin (HE) staining. Primary cultured human pulmonary artery smooth muscle cells (HPASMCs) were exposed to cigarette smoke extract (CSE). Cell proliferation was determined by cell counting and Methyl thiazolyl tetrazolium assay. Protein expression was analyzed by western blotting. Results: Morphometrical analysis showed that the pulmonary vessel wall thickness in smoker group and COPD group was significantly greater than that in nonsmoker group (P < .01). The protein level of ERK was significantly increased in smoker group and COPD group as compared with nonsmoker group (P < .01). The expression of ERK was significantly increased in HPASMCs at protein levels when HPASMCs were treated with 5% CSE (P < .01), which significantly promoted the proliferation of HPASMCs (P < .01). Conclusions: Increased expression of ERK might be involved in the pathogenesis of abnormal proliferation of PASMCs in smokers with and without COPD.