Liu Kui, Liu Xian-Sheng, Yu Mu-Qing, Xu Yong-Jian
Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Respiratory Disease, Ministry of Health, Wuhan, China.
Exp Lung Res. 2013 May-Jun;39(4-5):162-72. doi: 10.3109/01902148.2013.788234. Epub 2013 Apr 24.
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.
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.
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.
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).
Increased expression of ERK might be involved in the pathogenesis of abnormal proliferation of PASMCs in smokers with and without COPD.
吸烟可能通过导致涉及肺动脉平滑肌细胞（PASMC）增殖的肺血管重塑，进而促使慢性阻塞性肺疾病（COPD）患者发生肺动脉高压。然而，这一过程背后的分子机制仍知之甚少。
本研究旨在探究细胞外信号调节激酶（ERK）在肺功能正常的吸烟者以及轻度至中度COPD吸烟者的肺动脉中的作用。
从14名肺功能正常的非吸烟者、18名肺功能正常的吸烟者以及16名轻度至中度COPD吸烟者获取外周肺组织。通过苏木精-伊红（HE）染色观察肺动脉的形态学变化。将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）中。通过细胞计数和甲基噻唑基四氮唑法测定细胞增殖情况。通过蛋白质印迹法分析蛋白质表达。
形态计量学分析显示，吸烟者组和COPD组的肺血管壁厚度显著大于非吸烟者组（P <.01）。与非吸烟者组相比，吸烟者组和COPD组中ERK的蛋白质水平显著升高（P <.01）。当HPASMCs用5% CSE处理时，ERK在蛋白质水平上的表达显著增加（P <.01），这显著促进了HPASMCs的增殖（P <.01）。
ERK表达增加可能参与了有或无COPD的吸烟者中PASMCs异常增殖的发病机制。
