Transriptome Analysis of Peripheral Blood Monocytes in Chronic Obstructive Pulmonary Disease Patients.

IF 0.8 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Doklady Biochemistry and Biophysics Pub Date : 2024-10-31 DOI:10.1134/S1607672924701199

D E Naumov, O O Kotova, D A Gassan, I Yu Sugaylo, E G Sheludko, Y G Gorchakova

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引用次数: 0

Abstract

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.

Aim: : 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.

Materials and methods: . 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.

Results: : 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.

Conclusions: . 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.

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慢性阻塞性肺病患者外周血单核细胞的转录组分析

众所周知，单核细胞对慢性阻塞性肺病（COPD）的发生发展有重要作用；然而，人们对这些细胞的转录组与该疾病相关的特征仍然知之甚少：本研究旨在对单核细胞转录组进行分析，以确定慢性阻塞性肺病患者单核细胞中的差异表达基因和生物过程中的关键干扰。研究对象包括三名慢性阻塞性肺病患者和三名无支气管阻塞的吸烟者。采用塑料粘附法从外周血单核细胞中获得单核细胞。根据流式细胞术数据，富集后的细胞纯度约为 90%。从基因组 DNA 和核糖体 RNA 中纯化分离出 RNA 样本。样本在 MGISEQ-200 测序仪上以 SE50 模式进行测序。读数映射和转录本计数在 Salmon v1.10.1 软件中进行；进一步的数据处理在 R 软件环境中进行：分析结果显示，慢性阻塞性肺病患者的单核细胞中有 21 个上调基因和 29 个下调基因。在表达增加的基因中，最重要的是非编码 RNA PKD1P5-LOC105376752 和 PKD1P4-NPIPA8（其作用尚不清楚），以及 SETDB2、RNASE6、SERPINE1 和 MRC1。下调基因中，F8A2、ZDHHC19、CXCL9、CXCL10、HBA1、HBB、C2、CFB、CFD、MT1B、MT1G 和 TIMP3 最受关注，它们在七个基因本体（GO）术语中显示出富集，包括与脂多糖反应、过氧化氢、铜离子和补体激活有关的术语。所获得的数据表明，慢性阻塞性肺病患者的单核细胞功能活性受到抑制，其有效抵御微生物病原体的能力下降，同时对活性氧的自我保护能力减弱。SERPINE1的上调和TIMP3的下调可能是慢性阻塞性肺病患者气道重塑和肺气肿形成的重要原因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Doklady Biochemistry and Biophysics 生物-生化与分子生物学

CiteScore

1.60

自引率

12.50%

发文量

审稿时长

6-12 weeks

期刊介绍： Doklady Biochemistry and Biophysics is a journal consisting of English translations of articles published in Russian in biochemistry and biophysics sections of the Russian-language journal Doklady Akademii Nauk. The journal''s goal is to publish the most significant new research in biochemistry and biophysics carried out in Russia today or in collaboration with Russian authors. The journal accepts only articles in the Russian language that are submitted or recommended by acting Russian or foreign members of the Russian Academy of Sciences. The journal does not accept direct submissions in English.