EGR2 是心肌梗死的枢纽基因，可加重低氧诱导的心肌细胞炎症和凋亡。
EGR2 is a hub-gene in myocardial infarction and aggravates inflammation and apoptosis in hypoxia-induced cardiomyocytes.
机构信息
Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Chongqing Medical University, #76 Linjiang Road, Yuzhong District, Chongqing, 400010, China.
Research Base of Traditional Chinese Medicine Syndrome, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
出版信息
BMC Cardiovasc Disord. 2022 Aug 15;22(1):373. doi: 10.1186/s12872-022-02814-3.
BACKGROUND
Myocardial infarction (MI) is characterized by coronary artery occlusion, ischemia and hypoxia of myocardial cells, leading to irreversible myocardial damage. Therefore, it is urgent to explore the potential mechanism of myocardial injury during the MI process to develop effective therapies for myocardial cell rescue.
METHODS
We downloaded the GSE71906 dataset from GEO DataSets, and the R software was used to identify the differentially expressed genes (DEGs) in mouse heart tissues of MI and sham controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed to understand the significantly activated signaling pathways in MI. Protein-protein interaction (PPI) network was constructed to highlight the hub genes in DEGs. The Western Blot, qRT-PCR and TUNEL staining were used to explore the function of hub gene in hypoxia-induced cardiomyocytes in vitro.
RESULTS
A total of 235 DEGs were identified in GSE71906 dataset. Functional enrichment analysis revealed that the upregulated genes were primarily associated with the inflammatory response and apoptosis. 20 hub genes were identified in PPI network, and the early growth response 2 (EGR2) was highlighted. In vitro. We confirmed the EGR2 was upregulated induced by hypoxia and revealed the upregulated EGR2 aggravates pro-inflammation and pro-apoptotic genes expression. In addition, EGR2 knockout mitigates hypoxia-induced inflammation and apoptosis in cardiomyocytes.
CONCLUSION
The present study identified the EGR2 was a hub gene in myocardial damage during MI process, the excessive EGR2 aggravates hypoxia-induced myocardial damage by accelerating inflammation and apoptosis in vitro. Therefore, targeting EGR2 offers a potential pharmacological strategy for myocardial cell rescue in MI.
背景
心肌梗死（MI）的特征是冠状动脉阻塞、心肌细胞缺血缺氧，导致心肌不可逆损伤。因此，迫切需要探索 MI 过程中心肌损伤的潜在机制，以开发有效的心肌细胞保护治疗方法。
方法
我们从 GEO DataSets 下载了 GSE71906 数据集，使用 R 软件识别 MI 和假手术对照小鼠心脏组织中的差异表达基因（DEGs）。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，以了解 MI 中显著激活的信号通路。构建蛋白质-蛋白质相互作用（PPI）网络，突出 DEGs 中的枢纽基因。使用 Western Blot、qRT-PCR 和 TUNEL 染色来探索体外缺氧诱导的心肌细胞中枢纽基因的功能。
结果
在 GSE71906 数据集中鉴定出 235 个 DEGs。功能富集分析表明，上调基因主要与炎症反应和细胞凋亡有关。在 PPI 网络中鉴定出 20 个枢纽基因，其中早期生长反应 2（EGR2）被突出显示。在体外，我们证实缺氧诱导 EGR2 上调，并揭示上调的 EGR2 加剧促炎和促凋亡基因的表达。此外，EGR2 敲除减轻心肌细胞缺氧诱导的炎症和凋亡。
结论
本研究鉴定出 EGR2 是 MI 过程中心肌损伤的枢纽基因，过度的 EGR2 通过加速体外炎症和凋亡加重缺氧诱导的心肌损伤。因此，靶向 EGR2 为 MI 中的心肌细胞保护提供了一种潜在的药理学策略。
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