Upregulation of key genes Eln and Tgfb3 were associated with the severity of cardiac hypertrophy.
Upregulation of key genes Eln and Tgfb3 were associated with the severity of cardiac hypertrophy.
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关键基因 Eln 和 Tgfb3 的上调与心脏肥大的严重程度相关
DOI：
10.1186/s12864-022-08778-0
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发表时间：
2022-08-14
期刊：
影响因子：
4.4
通讯作者：
Li, Yongjun
中科院分区：
文献类型：
--
作者：
Zhang, Rui;Xu, Xuan;Chen, Xi;Hao, Chunshu;Ji, Zhenjun;Zuo, Pengfei;Yang, Mingming;Ma, Genshan;Li, Yongjun
高血压引起的心脏肥大是伴随心力衰竭的最常见的先决条件之一。本研究的目的是确定疾病过程中的关键致病基因。对GSE 18224进行再分析，获得差异表达基因（DEG）。进行了基因本体论（GO）和京都基因和基因组百科全书（KEGG）分析。构建转录因子（TF）-mRNA、微小RNA（miRNA）-mRNA和蛋白质相互作用（PPI）网络，并从PPI网络中筛选出关键模块。GSE 36074数据集和我们的横主动脉缩窄（TAC）小鼠模型用于验证模块中的基因表达。最后，对心肌肥厚相关基因和生物标志物之间的相关性进行了评价。GSE 18224中总共有348个DEG，主要富集在胶原纤维组织、细胞对转化生长因子β刺激的反应等生物学过程中，并参与ECM-受体相互作用和催产素信号通路。有387个miRNA被257个DEG靶向，而177个TF靶向71个DEG。PPI网络包含222个节点和770条边，其中18个基因被筛选到模块中。在验证之后，从18个DEG中选择在GSE 36074数据集中也显著上调的8个基因。在我们的小鼠心肌肥大模型中，8种DEG中的2种，包括Eln和Tgfb 3显著上调。最后，发现Eln和Tgfb 3的表达与疾病生物标志物的水平正相关。关键基因Eln和Tgfb 3的上调与心肌肥厚的严重程度呈正相关，可能为心肌肥厚的治疗提供潜在的靶点。在线版本包含补充材料，可通过10.1186/s12864-022-08778-0获得。
Hypertension-induced cardiac hypertrophy is one of the most common pre-conditions that accompanies heart failure. This study aimed to identify the key pathogenic genes in the disease process. GSE18224 was re-analyzed and differentially expressed genes (DEGs) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. Networks of transcription factor (TF)-mRNA, microRNA (miRNA)-mRNA and Protein-Protein interaction (PPI) were constructed, and a key module was further screened out from PPI network. GSE36074 dataset and our transverse aortic constriction (TAC) mouse model were used to validate gene expression in the module. Finally, the correlation between the genes and biomarkers of cardiac hypertrophy were evaluated. Totally, there were 348 DEGs in GSE18224, which were mainly enriched in biological processes including collagen fibril organization, cellular response to transforming growth factor-beta stimulus and were involved in ECM-receptor interaction and Oxytocin signaling pathway. There were 387 miRNAs targeted by 257 DEGs, while 177 TFs targeted 71 DEGs. The PPI network contained 222 nodes and 770 edges, with 18 genes screened out into the module. After validation, 8 genes, which were also significantly upregulated in the GSE36074 dataset, were selected from the 18 DEGs. 2 of the 8 DEGs, including Eln and Tgfb3 were significantly upregulated in our mouse model of myocardial hypertrophy. Finally, the expression of Eln and Tgfb3 were found to be positively correlated with the level of the disease biomarkers. Upregulated key genes Eln and Tgfb3 were positively correlated with the severity of cardiac hypertrophy, which may provide potential therapeutic targets for the disease. The online version contains supplementary material available at 10.1186/s12864-022-08778-0.
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