Reversible and permanent effects of tobacco smoke exposure on airway epithelial gene expression.
Reversible and permanent effects of tobacco smoke exposure on airway epithelial gene expression.
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DOI：
10.1186/gb-2007-8-9-r201
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发表时间：
2007
期刊：
影响因子：
12.3
通讯作者：
Spira A
中科院分区：
文献类型：
--
作者：
Beane J;Sebastiani P;Liu G;Brody JS;Lenburg ME;Spira A
寡核苷酸微阵列分析揭示了175个基因在目前吸烟的人与从不吸烟的人的大气道上皮细胞中差异表达，其中28个被归类为不可逆的，6个被归类为缓慢可逆的，139个被归类为快速可逆的。烟草使用仍然是美国可预防的主要死亡原因。对于戒烟多年的前吸烟者来说，死于与吸烟有关的疾病的风险仍然很高。烟草烟雾对气道基因表达的不可逆影响的鉴定可能为这种风险升高的原因提供见解。使用寡核苷酸微阵列，我们测量了大气道上皮细胞的基因表达，通过支气管镜从从来没有，目前，和以前的吸烟者（n = 104）。线性模型确定了175个基因在当前吸烟者和从不吸烟者之间差异表达，并根据其在前吸烟者中的表达将其分类为不可逆（n = 28），缓慢可逆（n = 6）或快速可逆（n = 139）。更大比例的不可逆和缓慢可逆的基因被吸烟下调，这表明持续变化的可能机制，如16q13的等位基因丢失。与其他环境暴露引起的气道上皮基因表达变化的相似性表明，共同的机制参与了烟草烟雾的反应。最后，使用不可逆基因，我们建立了一个暴露于烟草烟雾的生物标志物，能够对一组独立的前吸烟者和当前吸烟者进行分类，准确率分别为81%和100%。我们根据戒烟后气道基因表达的可逆性程度对吸烟相关变化进行了分类。我们的研究结果提供了对烟草烟雾可逆性和持续性影响机制的深入了解，这可能解释了前吸烟者患烟草诱导性肺病的风险增加，并为化学预防提供了新的靶点。气道基因表达也可以作为一个敏感的生物标志物，以确定个人与过去暴露于烟草烟雾。
Oligonucleotide microarray analysis revealed 175 genes that are differentially expressed in large airway epithelial cells of people who currently smoke compared with those who never smoked, with 28 classified as irreversible, 6 as slowly reversible, and 139 as rapidly reversible. Tobacco use remains the leading preventable cause of death in the US. The risk of dying from smoking-related diseases remains elevated for former smokers years after quitting. The identification of irreversible effects of tobacco smoke on airway gene expression may provide insights into the causes of this elevated risk. Using oligonucleotide microarrays, we measured gene expression in large airway epithelial cells obtained via bronchoscopy from never, current, and former smokers (n = 104). Linear models identified 175 genes differentially expressed between current and never smokers, and classified these as irreversible (n = 28), slowly reversible (n = 6), or rapidly reversible (n = 139) based on their expression in former smokers. A greater percentage of irreversible and slowly reversible genes were down-regulated by smoking, suggesting possible mechanisms for persistent changes, such as allelic loss at 16q13. Similarities with airway epithelium gene expression changes caused by other environmental exposures suggest that common mechanisms are involved in the response to tobacco smoke. Finally, using irreversible genes, we built a biomarker of ever exposure to tobacco smoke capable of classifying an independent set of former and current smokers with 81% and 100% accuracy, respectively. We have categorized smoking-related changes in airway gene expression by their degree of reversibility upon smoking cessation. Our findings provide insights into the mechanisms leading to reversible and persistent effects of tobacco smoke that may explain former smokers increased risk for developing tobacco-induced lung disease and provide novel targets for chemoprophylaxis. Airway gene expression may also serve as a sensitive biomarker to identify individuals with past exposure to tobacco smoke.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
56.9
作者：
Golub, TR;Slonim, DK;Lander, ES
通讯作者：
Lander, ES
影响因子：
11.5
作者：
Guo, MZ;House, MG;Brock, MV
通讯作者：
Brock, MV
影响因子：
4.8
作者：
Cowled, P;Kanter, I;Jackson, P
通讯作者：
Jackson, P
影响因子：
14.9
作者：
Harris, MA;Clark, J;White, R
通讯作者：
White, R