鉴定和验证与慢性阻塞性肺疾病衰老相关的遗传特征。
Identification and validation of genetic signature associated with aging in chronic obstructive pulmonary disease.
机构信息
Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Department of Science, Western University, London, Ontario N6A 3K7, Canada.
出版信息
Aging (Albany NY). 2022 Oct 28;14(20):8568-8580. doi: 10.18632/aging.204358.
Aging plays an essential role in the development for chronic obstructive pulmonary disease (COPD). The aim of this study was to identify and validate the potential aging-related genes of COPD through bioinformatics analysis and experimental validation. Firstly, we compared the gene expression profiles of aged and young COPD patients using two datasets (GSE76925 and GSE47460) from Gene Expression Omnibus (GEO), and identified 244 aging-related different expressed genes (DEGs), with 132 up-regulated and 112 down-regulated. Then, by analyzing the data for cigarette smoke-induced COPD mouse model (GSE125521), a total of 783 DEGs were identified between aged and young COPD mice, with 402 genes increased and 381 genes decreased. Additionally, functional enrichment analysis revealed that these DEGs were actively involved in COPD-related biological processes and function pathways. Meanwhile, six genes were identified as the core aging-related genes in COPD after combining the human DEGs and mouse DEGs. Eventually, five out of six core genes were validated to be up-regulated in the lung tissues collected from aged COPD patients than young COPD patients, namely NKG7, CKLF, LRP4, GDPD3 and CXCL9. Thereinto, the expressions of NKG7 and CKLF were negatively associated with lung function. These results may expand the understanding for aging in COPD.
衰老是慢性阻塞性肺疾病（COPD）发展的重要因素。本研究旨在通过生物信息学分析和实验验证，鉴定和验证 COPD 的潜在衰老相关基因。首先，我们使用来自基因表达综合数据库（GEO）的两个数据集（GSE76925 和 GSE47460）比较了老年和年轻 COPD 患者的基因表达谱，鉴定出 244 个与衰老相关的差异表达基因（DEGs），其中 132 个上调，112 个下调。然后，通过分析香烟烟雾诱导的 COPD 小鼠模型的数据（GSE125521），在老年和年轻 COPD 小鼠之间共鉴定出 783 个 DEGs，其中 402 个基因上调，381 个基因下调。此外，功能富集分析表明，这些 DEGs 积极参与 COPD 相关的生物学过程和功能途径。同时，将人类 DEGs 和小鼠 DEGs 结合后，鉴定出 6 个作为 COPD 中与衰老相关的核心基因。最终，在老年 COPD 患者的肺组织中验证了 6 个核心基因中的 5 个基因上调，即 NKG7、CKLF、LRP4、GDPD3 和 CXCL9。其中，NKG7 和 CKLF 的表达与肺功能呈负相关。这些结果可能扩展了对 COPD 中衰老的认识。
Zotero 插件