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基因网络方法揭示了鼻腔和支气管上皮中的共表达模式。

Gene network approach reveals co-expression patterns in nasal and bronchial epithelium.

机构信息

University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, The Netherlands.

University of Groningen, University Medical Center Groningen, GRIAC (Groningen Research Institute for Asthma and COPD), Groningen, The Netherlands.

出版信息

Sci Rep. 2019 Nov 1;9(1):15835. doi: 10.1038/s41598-019-50963-x.

DOI:10.1038/s41598-019-50963-x
PMID:31676779
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6825243/
Abstract

Nasal gene expression profiling is a new approach to investigate the airway epithelium as a biomarker to study the activity and treatment responses of obstructive pulmonary diseases. We investigated to what extent gene expression profiling of nasal brushings is similar to that of bronchial brushings. We performed genome wide gene expression profiling on matched nasal and bronchial epithelial brushes from 77 respiratory healthy individuals. To investigate differences and similarities among regulatory modules, network analysis was performed on correlated, differentially expressed and smoking-related genes using Gaussian Graphical Models. Between nasal and bronchial brushes, 619 genes were correlated and 1692 genes were differentially expressed (false discovery rate <0.05, |Fold-change|>2). Network analysis of correlated genes showed pro-inflammatory pathways to be similar between the two locations. Focusing on smoking-related genes, cytochrome-P450 pathway related genes were found to be similar, supporting the concept of a detoxifying response to tobacco exposure throughout the airways. In contrast, cilia-related pathways were decreased in nasal compared to bronchial brushes when focusing on differentially expressed genes. Collectively, while there are substantial differences in gene expression between nasal and bronchial brushes, we also found similarities, especially in the response to the external factors such as smoking.

摘要

鼻腔基因表达谱分析是一种新的方法,用于研究气道上皮细胞作为生物标志物,以研究阻塞性肺疾病的活性和治疗反应。我们研究了鼻腔刷检的基因表达谱在多大程度上与支气管刷检相似。我们对 77 名呼吸道健康个体的匹配鼻腔和支气管上皮刷检进行了全基因组基因表达谱分析。为了研究调控模块之间的差异和相似性,我们使用高斯图形模型对相关的、差异表达的和与吸烟相关的基因进行了网络分析。在鼻腔和支气管刷检之间,有 619 个基因相关,1692 个基因差异表达(错误发现率<0.05,|Fold-change|>2)。相关基因的网络分析显示,两个部位的促炎途径相似。关注与吸烟相关的基因,发现细胞色素 P450 途径相关基因相似,这支持了整个气道对烟草暴露的解毒反应的概念。相比之下,当关注差异表达的基因时,鼻刷中与纤毛相关的通路比支气管刷中减少。总的来说,虽然鼻腔和支气管刷检之间的基因表达存在很大差异,但我们也发现了相似之处,尤其是在外因如吸烟的反应方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6f7/6825243/21fdf8638775/41598_2019_50963_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6f7/6825243/fe1d38f8f1e4/41598_2019_50963_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6f7/6825243/29f217713ca4/41598_2019_50963_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6f7/6825243/483f8095ffe4/41598_2019_50963_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6f7/6825243/6187dc5e30a1/41598_2019_50963_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6f7/6825243/21fdf8638775/41598_2019_50963_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6f7/6825243/fe1d38f8f1e4/41598_2019_50963_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6f7/6825243/9cee12eed1c3/41598_2019_50963_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6f7/6825243/172f8fdc31c6/41598_2019_50963_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6f7/6825243/29f217713ca4/41598_2019_50963_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6f7/6825243/483f8095ffe4/41598_2019_50963_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6f7/6825243/6187dc5e30a1/41598_2019_50963_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6f7/6825243/21fdf8638775/41598_2019_50963_Fig7_HTML.jpg

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