转录组测序鉴定超重/肥胖高血压成人内脏脂肪组织关键基因。

IF 1.7 4区 生物学 Q4 CELL BIOLOGY
Cytogenetic and Genome Research Pub Date : 2022-01-01 Epub Date: 2022-12-15 DOI:10.1159/000528702
Lanlan Liao, Lihui Zhang, Hongping Chen, Da Teng, Bowen Xu, Lei Gong, Lin Zhong, Chunxiao Wang, Haibin Dong, Wenjuan Jia, Jun Yang, Zhen Shi
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引用次数: 0

摘要

超重和肥胖(OW/OB)成年人因内脏脂肪组织(VAT)炎症而患高血压的风险增加。在这项研究中,我们探讨了高血压和血压正常的OW/OB患者VAT的基因水平差异。对从6名OW/OB成人(3名高血压患者,3名血压正常患者)获得的VAT样本进行转录组测序分析。对所有基因表达数据进行基因集富集分析,以鉴定|log2(倍数变化)|≥1且q<0.05的差异表达基因(DEGs)。对DEG进行基因本体论和京都基因和基因组百科全书功能富集分析,并通过构建蛋白质-蛋白质相互作用(PPI)网络鉴定枢纽基因。在来自5名高血压患者和5名血压正常患者的10个其他样本中,使用定量实时PCR对所提出的枢纽基因进行了验证。此外,我们还进行了ROC分析和Spearman相关性分析。在患有和不患有高血压的OW/OB患者的VAT样本中,共鉴定出84个DEG,其中21个显著上调,63个显著下调。生物信息学分析显示,OW/OB成人的脾功能与高血压有关。同时,PPI网络分析确定了以下前10个枢纽基因:CD79A、CR2、SELL、CD22、IL7R、CCR7、TNFRSF13C、CXCR4、POU2AF1和JAK3。通过qPCR验证,我们发现CXCR4、CD22和IL7R具有统计学意义。qPCR验证表明RELA具有统计学意义。然而,qPCR验证表明,NFKB1和KLF2在统计学上不显著。这些枢纽基因主要受转录因子RELA的调控。CXCR4、IL7R和CD22的ROC分析的AUC为0.92。此外,VAT-CXCR4和CD22与RELA的相对表达水平呈正相关。总之,我们的研究表明,在高血压OW/OB成人中,与VAT相关的CXCR4、IL7R和CD22可以作为未来的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Identification of Key Genes from the Visceral Adipose Tissues of Overweight/Obese Adults with Hypertension through Transcriptome Sequencing.

Identification of Key Genes from the Visceral Adipose Tissues of Overweight/Obese Adults with Hypertension through Transcriptome Sequencing.

Identification of Key Genes from the Visceral Adipose Tissues of Overweight/Obese Adults with Hypertension through Transcriptome Sequencing.

Identification of Key Genes from the Visceral Adipose Tissues of Overweight/Obese Adults with Hypertension through Transcriptome Sequencing.

Overweight and obese (OW/OB) adults are at increased risk of hypertension due to visceral adipose tissue (VAT) inflammation. In this study, we explored gene level differences in the VAT of hypertensive and normotensive OW/OB patients. VAT samples obtained from six OW/OB adults (three hypertensive, three normotensive) were subjected to transcriptome sequencing analysis. Gene set enrichment analysis was conducted for all gene expression data to identify differentially expressed genes (DEGs) with |log2 (fold change)| ≥ 1 and q < 0.05. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses were performed on the DEGs, and hub genes were identified by constructing a protein-protein interaction (PPI) network. The proposed hub genes were validated using quantitative real-time PCR in ten other samples from five hypertensive and five normotensive patients. In addition, we performed ROC analysis and Spearman correlation analysis. A total of 84 DEGs were identified between VAT samples from OW/OB patients with and without hypertension, among which 21 were significantly upregulated and 63 were significantly downregulated. Bioinformatics analysis revealed that spleen function was related to hypertension in OW/OB adults. Meanwhile, PPI network analysis identified the following top 10 hub genes: CD79A, CR2, SELL, CD22, IL7R, CCR7, TNFRSF13C, CXCR4, POU2AF1, and JAK3. Through qPCR verification, we found that CXCR4, CD22, and IL7R were statistically significant. qPCR verification suggested that RELA was statistically significant. However, qPCR verification indicated that NFKB1 and KLF2 were not statistically significant. These hub genes were mainly regulated by the transcription factor RELA. The AUC of ROC analysis for CXCR4, IL7R, and CD22 was 0.92. What is more, VAT CXCR4 and CD22 were positively related to RELA relative expression levels. Taken together, our research demonstrates that CXCR4, IL7R, and CD22 related to VAT in hypertensive OW/OB adults could serve as future therapeutic targets.

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来源期刊
Cytogenetic and Genome Research
Cytogenetic and Genome Research 生物-细胞生物学
CiteScore
3.10
自引率
5.90%
发文量
25
审稿时长
1 months
期刊介绍: During the last decades, ''Cytogenetic and Genome Research'' has been the leading forum for original reports and reviews in human and animal cytogenetics, including molecular, clinical and comparative cytogenetics. In recent years, most of its papers have centered on genome research, including gene cloning and sequencing, gene mapping, gene regulation and expression, cancer genetics, comparative genetics, gene linkage and related areas. The journal also publishes key papers on chromosome aberrations in somatic, meiotic and malignant cells. Its scope has expanded to include studies on invertebrate and plant cytogenetics and genomics. Also featured are the vast majority of the reports of the International Workshops on Human Chromosome Mapping, the reports of international human and animal chromosome nomenclature committees, and proceedings of the American and European cytogenetic conferences and other events. In addition to regular issues, the journal has been publishing since 2002 a series of topical issues on a broad variety of themes from cytogenetic and genome research.
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