Naumov D E, Kotova O O, Gassan D A, Sugaylo I Yu, Sheludko E G, Gorchakova Y G
Far Eastern Scientific Center of Physiology and Pathology of Respiration, Blagoveshchensk, Russia.
Dokl Biochem Biophys. 2024 Dec;519(1):547-555. doi: 10.1134/S1607672924701199. Epub 2024 Oct 31.
It is known that monocytes can make a significant contribution to the development of chronic obstructive pulmonary disease (COPD); however, the features of the transcriptome of these cells associated with the disease remain poorly understood.
The aim of the study was to perform monocyte transcriptome analysis for identification of differentially expressed genes and key disturbances in biological processes in these cells in COPD.
The study included three COPD patients and three smokers without bronchial obstruction. Monocytes were obtained from peripheral blood mononuclear cells using the plastic adhesion method. The cell purity achieved as a result of enrichment was approximately 90% according to flow cytometry data. The isolated RNA samples were purified from genomic DNA and ribosomal RNA. The samples were sequenced on a MGISEQ-200 sequencer in SE50 mode. Read mapping and transcript counting were performed in Salmon v1.10.1 software; further data processing was carried out in R software environment.
As a result of the analysis, 21 upregulated and 29 downregulated genes were found in monocytes from COPD patients. Among the genes with increased expression, the most significant were the noncoding RNAs PKD1P5-LOC105376752 and PKD1P4-NPIPA8, the role of which remains unclear, as well as SETDB2, RNASE6, SERPINE1, and MRC1. Downregulated genes, of which F8A2, ZDHHC19, CXCL9, CXCL10, HBA1, HBB, C2, CFB, CFD, MT1B, MT1G, and TIMP3 were of most interest, showed enrichment in seven gene ontology (GO) terms, including those related to response to lipopolysaccharides, hydrogen peroxide, copper ions, and complement activation.
The data obtained indicate inhibition of monocyte functional activity in COPD patients with a decrease in the ability to provide effective protection against microbial pathogens while weakening self-protection against reactive oxygen species. Upregulation of SERPINE1 and downregulation of TIMP3 may significantly contribute to airway remodeling and emphysema development in COPD.
已知单核细胞对慢性阻塞性肺疾病（COPD）的发展有重大影响；然而，与该疾病相关的这些细胞转录组特征仍知之甚少。
本研究的目的是进行单核细胞转录组分析，以鉴定COPD患者这些细胞中差异表达的基因以及生物过程中的关键紊乱。
该研究纳入了三名COPD患者和三名无支气管阻塞的吸烟者。使用塑料贴壁法从外周血单核细胞中获取单核细胞。根据流式细胞术数据，富集后获得的细胞纯度约为90%。从基因组DNA和核糖体RNA中纯化分离出的RNA样本。样本在MGISEQ - 200测序仪上以SE50模式进行测序。在Salmon v1.10.1软件中进行读段比对和转录本计数；进一步的数据处理在R软件环境中进行。
分析结果显示，COPD患者单核细胞中有21个基因上调，29个基因下调。在表达增加的基因中，最显著的是非编码RNA PKD1P5 - LOC105376752和PKD1P4 - NPIPA8，其作用尚不清楚，还有SETDB2、RNASE6、SERPINE1和MRC1。下调的基因中，F8A2、ZDHHC19、CXCL9、CXCL10、HBA1、HBB、C2、CFB、CFD、MT1B、MT1G和TIMP3最受关注，这些基因在七个基因本体（GO）术语中富集，包括与对脂多糖、过氧化氢、铜离子的反应以及补体激活相关的术语。
获得的数据表明，COPD患者单核细胞功能活性受到抑制，提供针对微生物病原体的有效保护能力下降，同时对活性氧的自我保护减弱。SERPINE1的上调和TIMP3的下调可能对COPD患者气道重塑和肺气肿的发展有显著影响。
