Bioinformatics Program, Boston University, Boston, Massachusetts 02118, USA.
Physiol Genomics. 2010 Mar 3;41(1):1-8. doi: 10.1152/physiolgenomics.00167.2009. Epub 2009 Dec 1.
Previous studies have shown that physiological responses to cigarette smoke can be detected via bronchial airway epithelium gene expression profiling and that heterogeneity in this gene expression response to smoking is associated with lung cancer. In this study, we sought to determine the similarity of the effects of tobacco smoke throughout the respiratory tract by determining patterns of smoking-related gene expression in paired nasal and bronchial epithelial brushings collected from 14 healthy nonsmokers and 13 healthy current smokers. Using whole genome expression arrays, we identified 119 genes whose expression was affected by smoking similarly in both bronchial and nasal epithelium, including genes related to detoxification, oxidative stress, and wound healing. While the vast majority of smoking-related gene expression changes occur in both bronchial and nasal epithelium, we also identified 27 genes whose expression was affected by smoking more dramatically in bronchial epithelium than nasal epithelium. Both common and site-specific smoking-related gene expression profiles were validated using independent microarray datasets. Differential expression of select genes was also confirmed by RT-PCR. That smoking induces largely similar gene expression changes in both nasal and bronchial epithelium suggests that the consequences of cigarette smoke exposure can be measured in tissues throughout the respiratory tract. Our findings suggest that nasal epithelial gene expression may serve as a relatively noninvasive surrogate to measure physiological responses to cigarette smoke and/or other inhaled exposures in large-scale epidemiological studies.
先前的研究表明，通过支气管气道上皮细胞基因表达谱可以检测到对香烟烟雾的生理反应，并且这种吸烟引起的基因表达反应的异质性与肺癌有关。在这项研究中，我们试图通过确定从 14 名健康非吸烟者和 13 名健康当前吸烟者收集的配对鼻和支气管上皮刷取物中与吸烟相关的基因表达模式，来确定整个呼吸道中烟草烟雾的影响的相似性。使用全基因组表达谱芯片，我们鉴定了 119 个基因，这些基因在支气管和鼻上皮中受到吸烟的相似影响，包括与解毒、氧化应激和伤口愈合相关的基因。虽然绝大多数与吸烟相关的基因表达变化发生在支气管和鼻上皮中，但我们也鉴定了 27 个基因，这些基因在支气管上皮中受吸烟影响比鼻上皮更显著。使用独立的微阵列数据集验证了常见和特定部位的与吸烟相关的基因表达谱。通过 RT-PCR 也证实了选择基因的差异表达。吸烟在鼻和支气管上皮中引起相似的基因表达变化，这表明可以在整个呼吸道的组织中测量香烟烟雾暴露的后果。我们的发现表明，鼻上皮基因表达可能作为一种相对非侵入性的替代方法，用于在大规模的流行病学研究中测量对香烟烟雾和/或其他吸入性暴露的生理反应。
