Transcriptomic analysis of key genes and signaling pathways in sepsis-associated intestinal mucosal barrier damage

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene Pub Date : 2025-02-05 DOI:10.1016/j.gene.2024.149137

Zhao Gao , Zhiyuan Gong , Hai Huang , Xuemeng Ren , Zhenlu Li , Peng Gao

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引用次数: 0

Abstract

Objectives

The aim is to analyze differentially expressed genes (DEGs) in mice with sepsis-related intestinal mucosal barrier damage and to explore the diagnostic and protective mechanisms of this condition at the transcriptome level.

Methods

Small intestinal tissues from healthy male C57BL/6J mice subjected to Cecal ligation and puncture (CLP) and sham operation were collected. High-throughput sequencing was performed using the paired-end sequencing mode of the Illumina HiSeq platform. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted on the differentially expressed genes (DEGs). A protein–protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified with Cytoscape. These hub genes were then validated using quantitative real-time polymerase chain reaction (RT-qPCR).

Results

A total of 239 DEGs were identified, with 49 upregulated and 130 downregulated genes. KEGG enrichment analysis showed that these DEGs were primarily involved in cytokine-cytokine receptor interaction, Th1 and Th2 cell differentiation, viral protein interactions with cytokines and their receptors, and the IL-17 signaling pathway. The top 10 hub genes were selected using the cytoHubba plugin. Experimental validation confirmed that the expression levels of TBX21, CSF3, IL-6, CXCR3, and CXCL9 matched the sequencing results.

Conclusion

TBX21, CSF3, IL-6,CXCR3, and CXCL9 may be potential biological markers for the diagnosis and treatment the sepsis-associated intestinal mucosal barrier.

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脓毒症相关肠黏膜屏障损伤关键基因和信号通路的转录组学分析。

目的：分析脓毒症相关肠黏膜屏障损伤小鼠的差异表达基因（DEGs），并从转录组水平探讨其诊断和保护机制。方法：收集经盲肠结扎穿刺（CLP）和假手术治疗的健康雄性C57BL/6J小鼠小肠组织。采用Illumina HiSeq平台的对端测序模式进行高通量测序。对差异表达基因（DEGs）进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析。利用STRING数据库构建蛋白-蛋白相互作用（PPI）网络，并利用Cytoscape对枢纽基因进行鉴定。然后使用实时定量聚合酶链反应（RT-qPCR）验证这些中心基因。结果：共鉴定出239个deg，其中上调基因49个，下调基因130个。KEGG富集分析表明，这些deg主要参与细胞因子-细胞因子受体相互作用、Th1和Th2细胞分化、病毒蛋白与细胞因子及其受体的相互作用以及IL-17信号通路。使用cytoHubba插件选择前10个枢纽基因。实验验证TBX21、CSF3、IL-6、CXCR3、CXCL9的表达水平与测序结果相符。结论：TBX21、CSF3、IL-6、CXCR3、CXCL9可能是诊断和治疗脓毒症相关肠黏膜屏障的潜在生物学标志物。

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

Gene 生物-遗传学

CiteScore

6.10

自引率

2.90%

发文量

718

审稿时长

42 days

期刊介绍： Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.