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利用RNA测序鉴定盐敏感性高血压的生物标志物、信号通路及潜在治疗药物

Identification of biomarkers, pathways and potential therapeutic agents for salt-sensitive hypertension using RNA-seq.

作者信息

Chao Xiaoying, Jiang Zhiyuan, Zhong Guoqiang, Huang Rongjie

机构信息

Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Division of Hypertension, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

出版信息

Front Cardiovasc Med. 2022 Aug 10;9:963744. doi: 10.3389/fcvm.2022.963744. eCollection 2022.

DOI:10.3389/fcvm.2022.963744
PMID:36035920
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9399395/
Abstract

BACKGROUND

Salt-sensitive hypertension (SSH) is a common type of essential hypertension in China. In recent years, although an increasing number of researches have focused on SSH, few studies have been researched on patients with SSH. The objective of this study was to explore the genes and pathways linked with SSH using RNA-sequencing (RNA-seq).

MATERIALS AND METHODS

We used RNA-seq to analyze the transcriptome of peripheral blood mononuclear cells (PBMCs) of five SSH patients and five SRH patients. Next, we analyzed the differentially expressed genes (DEGs) using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Set Enrichment (GSEA) enrichment analysis. Then, Cytoscape was used to construct the protein-protein interaction (PPI) network and the hub genes. Finally, CMAP analysis found that several small molecular compounds could reverse the altered DEGs.

RESULTS

A total of 431 DEGs were found in the PBMC samples, including 294 up-regulated and 137 down-regulated genes. Functional enrichment analysis found significant enrichment in immune-related associations such as inflammation, chemokine, and cytokine-cytokine receptor interaction. The hub genes of the two modules were IL-6, IL-1A, CCL2, CCL3L3, and BUB1. In addition, we identified two small molecular compounds (iopromide and iloprost) that potentially interacted with DEGs.

CONCLUSION

This study suggests some potential biomarkers for the diagnosis of SSH. It provides new insights into SSH diagnosis and possible future clinical treatment.

摘要

背景

盐敏感性高血压(SSH)是中国原发性高血压的常见类型。近年来,尽管越来越多的研究聚焦于SSH,但针对SSH患者的研究较少。本研究的目的是利用RNA测序(RNA-seq)探索与SSH相关的基因和通路。

材料与方法

我们使用RNA-seq分析了5例SSH患者和5例盐抵抗性高血压(SRH)患者外周血单个核细胞(PBMC)的转录组。接下来,我们使用基因本体(GO)、京都基因与基因组百科全书(KEGG)通路以及基因集富集(GSEA)分析来分析差异表达基因(DEG)。然后,使用Cytoscape构建蛋白质-蛋白质相互作用(PPI)网络和枢纽基因。最后,通过连通图(CMAP)分析发现几种小分子化合物可以逆转DEG的变化。

结果

在PBMC样本中共发现431个DEG,包括294个上调基因和137个下调基因。功能富集分析发现,在炎症、趋化因子和细胞因子-细胞因子受体相互作用等免疫相关关联中存在显著富集。两个模块的枢纽基因是白细胞介素-6(IL-6)、白细胞介素-1A(IL-1A)、趋化因子配体2(CCL2)、趋化因子配体3L3(CCL3L3)和BUB1。此外,我们鉴定出两种可能与DEG相互作用的小分子化合物(碘普罗胺和伊洛前列素)。

结论

本研究提出了一些用于SSH诊断的潜在生物标志物。它为SSH诊断和未来可能的临床治疗提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/2afaca08320a/fcvm-09-963744-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/8b44e01fde1b/fcvm-09-963744-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/6248296ab55b/fcvm-09-963744-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/ad77db91e397/fcvm-09-963744-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/b268691fb0e1/fcvm-09-963744-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/2cdcb2a8d93b/fcvm-09-963744-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/1a7498ea573d/fcvm-09-963744-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/b6fa4a55cd88/fcvm-09-963744-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/2afaca08320a/fcvm-09-963744-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/8b44e01fde1b/fcvm-09-963744-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/6248296ab55b/fcvm-09-963744-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/ad77db91e397/fcvm-09-963744-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/b268691fb0e1/fcvm-09-963744-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/2cdcb2a8d93b/fcvm-09-963744-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/1a7498ea573d/fcvm-09-963744-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/b6fa4a55cd88/fcvm-09-963744-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/9399395/2afaca08320a/fcvm-09-963744-g008.jpg

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