Identification and validation of genetic signature associated with aging in chronic obstructive pulmonary disease.

Identification and validation of genetic signature associated with aging in chronic obstructive pulmonary disease.
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慢性阻塞性肺疾病衰老相关基因特征的鉴定和验证。

DOI:
10.18632/aging.204358
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发表时间:
2022-10-28
期刊:
影响因子:
5.2
通讯作者:
Xie, Jungang
Xie, Jungang
中科院分区:
医学2区
文献类型:
--
作者:
Chen, Shanshan;Zhan, Yuan;Chen, Jinkun;Wu, Jixing;Gu, Yiya;Huang, Qian;Deng, Zhesong;Wu, Xiaojie;Lv, Yongman;Xie, Jungang

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衰老在慢性阻塞性肺疾病(COPD)的发展中起着至关重要的作用。本研究的目的是通过生物信息学分析和实验验证,筛选和验证COPD潜在的衰老相关基因。首先,我们利用基因表达数据库(Gene Expression Omnibus,GEO)中的两个数据集(GSE 76925和GSE 47460)比较了老年和青年COPD患者的基因表达谱,发现了244个与衰老相关的差异表达基因(DEG),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(GSE 125521)的数据,在老年和青年COPD小鼠中总共鉴定出783个DEG,其中402个基因增加,381个基因减少。此外,功能富集分析显示,这些DEG积极参与COPD相关的生物学过程和功能途径。同时,将人和小鼠的DEGs结合起来,筛选出6个与COPD衰老相关的核心基因。最终,六个核心基因中的五个被证实在从老年COPD患者收集的肺组织中比年轻COPD患者上调,即NKG 7、CKLF、LRP 4、GDPD 3和CXCL 9。其中NKG 7和CKLF的表达与肺功能呈负相关。这些结果可能扩大对COPD衰老的理解。
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.
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