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基于转录组测序的 LPS/D-GalN 诱导的小鼠急性肝衰竭相关关键免疫相关基因的鉴定。

Identification of key immune-related genes associated with LPS/D-GalN-induced acute liver failure in mice based on transcriptome sequencing.

机构信息

Department of Infectious Disease, Zhejiang Hospital, Hangzhou, China.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

出版信息

PeerJ. 2023 May 5;11:e15241. doi: 10.7717/peerj.15241. eCollection 2023.

DOI:10.7717/peerj.15241
PMID:37168540
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10166078/
Abstract

BACKGROUND

The aim of this study was to identify key immune-related genes in acute liver failure (ALF) by constructing an ALF mouse model for transcriptome sequencing.

METHODS

The C57BL/6 mouse with ALF model was induced by lipopolysaccharide (LPS)/ D-galactosamine (D-GalN). After successful modelling, the liver tissues of all mice were obtained for transcriptome sequencing. The key immune-related genes in mice with ALF were identified by differential expression analysis, immune infiltration analysis, weighted gene co-expression network analysis (WGCNA), enrichment analysis, and protein-protein interaction (PPI) analysis.

RESULTS

An LPS/D-GalN-induced ALF mouse model was successfully constructed, and transcriptome sequencing was performed. Significant differences in the proportions of monocytes, macrophages M0, macrophages M1 and neutrophils were shown by immune infiltration analysis, and 5255 genes highly associated with these four immune cells were identified by WGCNA. These immune genes were found to be significantly enriched in the TNF signalling pathway by enrichment analysis. Finally, PPI analysis was performed on genes enriched in this pathway and three key genes (CXCL1, CXCL10 and IL1B) were screened out and revealed to be significantly upregulated in ALF.

CONCLUSIONS

Key immune-related genes in ALF were identified in this study, which may provide not only potential therapeutic targets for treating ALF and improving its prognosis, but also a reliable scientific basis for the immunotherapy of the disease.

摘要

背景

本研究旨在通过构建急性肝衰竭（ALF）小鼠转录组测序模型，鉴定关键的免疫相关基因。

方法

采用脂多糖（LPS）/D-半乳糖胺（D-GalN）诱导 C57BL/6 小鼠建立 ALF 模型。成功建模后，获取所有小鼠的肝组织进行转录组测序。通过差异表达分析、免疫浸润分析、加权基因共表达网络分析（WGCNA）、富集分析和蛋白质-蛋白质相互作用（PPI）分析，鉴定 ALF 小鼠中的关键免疫相关基因。

结果

成功构建了 LPS/D-GalN 诱导的 ALF 小鼠模型，并进行了转录组测序。免疫浸润分析显示单核细胞、M0 巨噬细胞、M1 巨噬细胞和中性粒细胞的比例存在显著差异，WGCNA 鉴定出与这四种免疫细胞高度相关的 5255 个基因。富集分析显示这些免疫基因显著富集在 TNF 信号通路中。最后，对该通路中富集的基因进行 PPI 分析，筛选出三个关键基因（CXCL1、CXCL10 和 IL1B），并发现它们在 ALF 中显著上调。

结论

本研究鉴定了 ALF 中的关键免疫相关基因，这不仅为治疗 ALF 和改善其预后提供了潜在的治疗靶点，也为该病的免疫治疗提供了可靠的科学依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c5/10166078/f6dce1673018/peerj-11-15241-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c5/10166078/f6dce1673018/peerj-11-15241-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c5/10166078/120c22c76a38/peerj-11-15241-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c5/10166078/015170e031c0/peerj-11-15241-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c5/10166078/f6dce1673018/peerj-11-15241-g008.jpg

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