转录组分析和加权基因共表达网络分析揭示了大鼠深低温停循环后肺组织中枢纽基因和分子通路的变化。

Transcriptome profiling and weighted gene co-expression network analysis reveal changes of hub genes and molecular pathways in rat lungs following deep hypothermic circulatory arrest.

作者信息

Wang Lei, Wu Qingtong, Lin Yuzuo, Lin Ziyan, Zhong Guodong, Chen Liangwan

机构信息

Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, China.

Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China.

出版信息

PLoS One. 2025 Aug 14;20(8):e0328887. doi: 10.1371/journal.pone.0328887. eCollection 2025.

DOI:10.1371/journal.pone.0328887

PMID:40811488

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12352637/

Abstract

BACKGROUND

The incidence of acute lung injury (ALI) following aortic dissection repair surgery that involves deep hypothermic circulatory arrest (DHCA) is notably high. We analyzed hub genes and signaling pathways in rat lung tissues post-DHCA using transcriptome sequencing and weighted gene co-expression network analysis (WGCNA).

METHODS

A rat model of DHCA was established, and lung tissues were collected after the procedure. High-throughput transcriptome sequencing was employed to assess gene expression differences between the DHCA group and the non-DHCA group. The DESeq2 method was utilized to analyze differentially expressed genes (DEGs) between these two groups, with further screening for hub genes and their upstream molecules conducted using WGCNA, protein-protein interaction (PPI) networks, and the iRegulon plugin. Biological functions of hub genes were examined via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The changes in mRNA and protein levels of hub genes across both groups were evaluated through experimental verification.

RESULTS

A total of 438 DEGs were identified when comparing the DHCA group to the control group. WGCNA further revealed 197 key genes. Subsequent PPI analysis led to the identification of eight hub genes: FOS, FOSB, JUN, EGR1, ATF3, NR4A1, CCN1, and ZFP36. The hub genes were primarily associated with inflammation, cell apoptosis, and cellular immune responses. ATF3 and SRF may serve as potential upstream regulators. The experimental findings further corroborated that substantial alterations took place in these hub genes, accompanied by significant injury of lung tissue during DHCA.

CONCLUSION

DHCA significantly altered gene expression patterns in rat lung tissues. The identified hub genes and signaling pathways related to inflammation and apoptosis may serve as potential therapeutic targets for lung injury following DHCA.

摘要

背景

在涉及深低温循环停搏（DHCA）的主动脉夹层修复手术后，急性肺损伤（ALI）的发生率显著较高。我们使用转录组测序和加权基因共表达网络分析（WGCNA）分析了DHCA后大鼠肺组织中的枢纽基因和信号通路。

方法

建立DHCA大鼠模型，术后收集肺组织。采用高通量转录组测序评估DHCA组和非DHCA组之间的基因表达差异。利用DESeq2方法分析两组之间的差异表达基因（DEG），并使用WGCNA、蛋白质-蛋白质相互作用（PPI）网络和iRegulon插件进一步筛选枢纽基因及其上游分子。通过基因本体论和京都基因与基因组百科全书分析来研究枢纽基因的生物学功能。通过实验验证评估两组中枢纽基因的mRNA和蛋白质水平变化。

结果

将DHCA组与对照组比较时，共鉴定出438个DEG。WGCNA进一步揭示了197个关键基因。随后的PPI分析确定了8个枢纽基因：FOS、FOSB、JUN、EGR1、ATF3、NR4A1、CCN1和ZFP36。这些枢纽基因主要与炎症、细胞凋亡和细胞免疫反应相关。ATF3和SRF可能作为潜在的上游调节因子。实验结果进一步证实，在DHCA期间这些枢纽基因发生了显著变化，同时伴有肺组织的明显损伤。