PDF(Pubmed)
Abstract：
Chronic obstructive pulmonary disease (COPD) is commonly caused from smoking cigarettes that induce biological stress responses. Previously we found disorganized endoplasmic reticulum (ER) in fibroblasts from COPD with different responses to chemical stressors compared to healthy subjects. Here, we aimed to investigate differences in stress-related gene expressions within lung cells from COPD and healthy subjects. Bronchoalveolar lavage (BAL) cells were collected from seven COPD and 35 healthy subjects. Lung fibroblasts were derived from 19 COPD and 24 healthy subjects and exposed to cigarette smoke extract (CSE). Gene and protein expression and cell proliferation were investigated. Compared to healthy subjects, we found lower gene expression of CHOP in lung fibroblasts from COPD subjects. Exposure to CSE caused inhibition of lung fibroblast proliferation in both groups, though the changes in ER stress-related gene expressions (ATF6, IRE1, PERK, ATF4, CHOP, BCL2L1) and genes relating to proteasomal subunits mostly occurred in healthy lung fibroblasts. No differences were found in BAL cells. In this study, we have found that lung fibroblasts from COPD subjects have an atypical ER stress gene response to CSE, particularly in genes related to apoptosis. This difference in response to CSE may be a contributing factor to COPD progression.
摘要：
慢性阻塞性肺疾病（COPD）通常是由吸烟引起的生物应激反应引起的。以前，我们发现与健康受试者相比，COPD成纤维细胞对化学应激源的反应不同，内质网（ER）紊乱。这里,我们旨在研究COPD和健康受试者肺细胞内应激相关基因表达的差异.从7名COPD和35名健康受试者收集支气管肺泡灌洗(BAL)细胞。肺成纤维细胞来自19名COPD和24名健康受试者，并暴露于香烟烟雾提取物（CSE）。研究了基因和蛋白质表达以及细胞增殖。与健康受试者相比，我们发现COPD患者肺成纤维细胞中CHOP基因表达较低.暴露于CSE导致两组肺成纤维细胞增殖的抑制，尽管内质网应激相关基因表达的变化(ATF6，IRE1，PERK，ATF4,CHOP,BCL2L1）和与蛋白酶体亚基相关的基因主要发生在健康肺成纤维细胞中。在BAL细胞中没有发现差异。在这项研究中,我们发现COPD受试者的肺成纤维细胞对CSE有非典型的ER应激基因反应，特别是与细胞凋亡相关的基因。对CSE反应的这种差异可能是COPD进展的一个促成因素。
