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ox-LDL 作用下内皮细胞 mRNA 谱的测序分析

Sequencing Analysis of mRNA Profile in Endothelial Cells in Response to ox-LDL.

机构信息

Department of Genetics, Center for Genetics, National Research Institute for Family Planning, 12, Dahuisi Road, Haidian, Beijing, 100081, China.

Graduate School, Peking Union Medical College, Beijing, 100081, China.

出版信息

Biochem Genet. 2021 Jun;59(3):767-780. doi: 10.1007/s10528-021-10028-z. Epub 2021 Feb 2.

Abstract

The pathogenesis of atherosclerosis (AS) and abnormal endothelial cells apoptosis is a multifactorial biological process. Oxidized low density lipoprotein (ox-LDL) is a critical factor in the formation of AS. However, the exact mechanism is still not clear. Therefore, the aim of this study was to investigate some genes and biological pathways in endothelial cells apoptosis in response to ox-LDL. First, our results has validated that ox-LDL is an effective inducer of endothelial cells apoptosis, then, transcriptome sequencing was used to detect differential expression genes. In total, 71 differentially expressed genes (DEGs) were identified, including 32 upregulated genes and 39 downregulated genes. GO analysis showed that DEGs were mainly enriched in cytokine-mediated signaling pathway, gene expression, external side of plasma membrane, steroid binding, and signaling receptor binding. After KEGG analysis, the DEGs mainly focused on the following biochemical signaling pathways, including Signaling molecules and interaction (such as ICOSLG, IL6, ITGAM, TNFRSF13C and VTCN1), Signal transduction (such as IL13RA2, IL6, ITGAM, PDE5A, SGK3 and TNFRSF13C), Immune system (such as FCGR2A, ICOSLG, IL6, ITGAM and TNFRSF13C), and so on. These genes may play a dominant role in HAECs apoptosis and AS genesis. The above prediction and analysis provide an important basis for our follow-up study of the mechanism of these genes, which might be used as molecular targets or diagnostic biomarkers for AS.

摘要

动脉粥样硬化(AS)的发病机制和异常内皮细胞凋亡是一个多因素的生物学过程。氧化型低密度脂蛋白(ox-LDL)是 AS 形成的关键因素。然而,确切的机制尚不清楚。因此,本研究旨在探讨 ox-LDL 诱导内皮细胞凋亡过程中相关基因和生物途径。首先,我们的结果验证了 ox-LDL 是内皮细胞凋亡的有效诱导剂,然后使用转录组测序检测差异表达基因。总共鉴定出 71 个差异表达基因(DEGs),包括 32 个上调基因和 39 个下调基因。GO 分析表明,DEGs 主要富集在细胞因子介导的信号通路、基因表达、质膜外侧、类固醇结合和信号受体结合等方面。KEGG 分析后,DEGs 主要集中在以下生化信号通路,包括信号分子和相互作用(如 ICOSLG、IL6、ITGAM、TNFRSF13C 和 VTCN1)、信号转导(如 IL13RA2、IL6、ITGAM、PDE5A、SGK3 和 TNFRSF13C)、免疫系统(如 FCGR2A、ICOSLG、IL6、ITGAM 和 TNFRSF13C)等。这些基因可能在 HAECs 凋亡和 AS 发病机制中起主导作用。上述预测和分析为我们后续研究这些基因的机制提供了重要依据,这些基因可能作为 AS 的分子靶点或诊断生物标志物。

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