扩张型心肌病中炎症反应基因的表达谱及潜在调控机制。
Expression Profile of Inflammation Response Genes and Potential Regulatory Mechanisms in Dilated Cardiomyopathy.
机构信息
Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China.
出版信息
Oxid Med Cell Longev. 2022 Aug 17;2022:1051652. doi: 10.1155/2022/1051652. eCollection 2022.
BACKGROUND
The inflammatory response is important in dilated cardiomyopathy (DCM). However, the expression of inflammatory response genes (IRGs) and regulatory mechanisms in DCM has not been well characterized.
METHODS
We analyzed 27,665 cells of single-cell RNA sequencing dataset of four DCM samples and two healthy controls (HC). IRGs among differentially expressed genes (DEGs) of active cell clusters were screened from the Molecular Signatures Database (MSigDB). The bulk sequencing dataset of 166 DCM patients and 166 HC was analyzed to explore the common IRGs. The biological functions of the IRGs were analyzed according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. IRG-related transcription factors (TFs) were determined using the TRRUST database. The protein-protein interaction (PPI) network was constructed using the STRING database. Then, we established the noncoding RNA (ncRNA) regulatory network based on the StarBase database. Finally, the potential drugs that target IRGs were explored using the Drug Gene Interaction Database (DGIdb).
RESULTS
The proportions of dendritic cells (DCs), B cells, NK cells, and T cells were increased in DCM patients, whereas monocytes were decreased. DCs expressed more IRGs in DCM. The GO and KEGG analyses indicated that the functional characteristics of active cells mainly focused on the immune response. Thirty-nine IRGs were commonly expressed among active cell cluster DEGs, bulk RNA DEGs, and inflammatory response-related genes. ETS1 plays an important role in regulation of IRG expression. The competing endogenous RNA regulatory network showed the relationship between ncRNA and IRGs. Sankey diagram showed that arachidonate 5-lipoxygenase (ALOX5) played a major role in regulation between TFs and potential drugs.
CONCLUSION
DCs infiltrate into the myocardium and contribute to the immune response in DCM. The transcription factor ETS1 plays an important role in regulation of IRGs. Moreover, may be a potential therapeutic target for DCM.
背景
炎症反应在扩张型心肌病（DCM）中很重要。然而，DCM 中炎症反应基因（IRGs）的表达和调控机制尚未得到很好的描述。
方法
我们分析了四个 DCM 样本和两个健康对照（HC）的单细胞 RNA 测序数据集的 27665 个细胞。从分子特征数据库（MSigDB）中筛选出活跃细胞簇中差异表达基因（DEGs）中的 IRGs。分析了 166 例 DCM 患者和 166 例 HC 的批量测序数据集，以探讨常见的 IRGs。根据基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析，对 IRGs 的生物学功能进行了分析。使用 TRRUST 数据库确定 IRG 相关转录因子（TFs）。使用 STRING 数据库构建蛋白质-蛋白质相互作用（PPI）网络。然后，我们基于 StarBase 数据库构建了非编码 RNA（ncRNA）调控网络。最后，使用药物基因相互作用数据库（DGIdb）探索了针对 IRGs 的潜在药物。
结果
DCM 患者的树突状细胞（DCs）、B 细胞、NK 细胞和 T 细胞比例增加，而单核细胞减少。DCs 在 DCM 中表达更多的 IRGs。GO 和 KEGG 分析表明，活跃细胞的功能特征主要集中在免疫反应上。在活跃细胞簇 DEGs、批量 RNA DEGs 和炎症反应相关基因中，有 39 个 IRG 共同表达。ETS1 在调节 IRG 表达中起着重要作用。竞争内源性 RNA 调控网络显示了 ncRNA 与 IRGs 之间的关系。Sankey 图显示，花生四烯酸 5-脂氧合酶（ALOX5）在 TF 和潜在药物之间的调节中起主要作用。
结论
DC 浸润到心肌中，在 DCM 中引起免疫反应。转录因子 ETS1 在调节 IRGs 中起着重要作用。此外，可能是 DCM 的一个潜在治疗靶点。
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