Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 210009, Nanjing, P. R. China.
BMC Genomics. 2022 Aug 14;23(1):592. doi: 10.1186/s12864-022-08778-0.
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.
高血压引起的心肌肥厚是心力衰竭最常见的伴发疾病之一。本研究旨在确定该疾病过程中的关键致病基因。
重新分析 GSE18224 数据集并获得差异表达基因（DEGs）。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。构建转录因子（TF）-mRNA、microRNA（miRNA）-mRNA 和蛋白质-蛋白质相互作用（PPI）网络，并从 PPI 网络中进一步筛选出关键模块。使用 GSE36074 数据集和我们的主动脉缩窄（TAC）小鼠模型验证模块中的基因表达。最后，评估基因与心肌肥厚生物标志物之间的相关性。
在 GSE18224 中共有 348 个 DEGs，其主要富集于生物学过程，包括胶原纤维组织、细胞对转化生长因子-β刺激的反应，并参与细胞外基质受体相互作用和催产素信号通路。有 257 个 DEGs 靶向 387 个 miRNA，而 177 个 TF 靶向 71 个 DEGs。PPI 网络包含 222 个节点和 770 个边，从中筛选出 18 个基因组成模块。经过验证，从 18 个 DEGs 中选择了 8 个在 GSE36074 数据集中也显著上调的基因。在我们的心肌肥厚小鼠模型中，这 8 个 DEGs 中有 2 个（Eln 和 Tgfb3）显著上调。最后，发现 Eln 和 Tgfb3 的表达与疾病生物标志物的水平呈正相关。
上调的关键基因 Eln 和 Tgfb3 与心肌肥厚的严重程度呈正相关，这可能为该疾病提供潜在的治疗靶点。
