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共识基因网络分析鉴定了感染后内皮细胞和上皮细胞动力学的关键相似性和差异。

Consensus Gene Network Analysis Identifies the Key Similarities and Differences in Endothelial and Epithelial Cell Dynamics after Infection.

机构信息

Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38103, USA.

Center for Biomedical Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38103, USA.

出版信息

Int J Mol Sci. 2023 Jul 21;24(14):11748. doi: 10.3390/ijms241411748.

Abstract

Endothelial and epithelial cells are morphologically different and play a critical role in host defense during infection. Both cells respond to infection by activating various signaling pathways and gene expression patterns. Their interactions with these pathogens can have beneficial and detrimental effects, and a better understanding of these interactions can help guide the development of new therapies for infection. To identify the differences and similarities between human endothelial and oral epithelial cell transcriptomics during infection, we performed consensus WGCNA on 32 RNA-seq samples by relating the consensus modules to endothelial-specific modules and analyzing the genes connected. This analysis resulted in the identification of 14 distinct modules. We demonstrated that the magenta module correlates significantly with infection in each dataset. In addition, we found that the blue and cyan modules in the two datasets had opposite correlation coefficients with a infection. However, the correlation coefficients and -values between the two datasets were slightly different. Functional analyses of the hub of genes from endothelial cells elucidated the enrichment in TNF, AGE-RAGE, MAPK, and NF-κB signaling. On the other hand, glycolysis, pyruvate metabolism, amino acid, fructose, mannose, and vitamin B6 metabolism were enriched in epithelial cells. However, mitophagy, necroptosis, apoptotic processes, and hypoxia were enriched in both endothelial and epithelial cells. Protein-protein interaction analysis using STRING and CytoHubba revealed , , , and as endothelial hub genes, while , , , and genes were identified in epithelial cells. Understanding these similarities and differences may provide new insights into the pathogenesis of infections and the development of new therapeutic targets and interventional strategies.

摘要

内皮细胞和上皮细胞在形态上有所不同,在感染期间对宿主防御起着至关重要的作用。这两种细胞通过激活各种信号通路和基因表达模式来应对感染。它们与这些病原体的相互作用可能既有有益的,也有有害的,更好地了解这些相互作用可以帮助指导针对感染的新疗法的开发。为了确定人类内皮细胞和口腔上皮细胞在感染期间转录组学的异同,我们通过将共识模块与内皮细胞特异性模块相关联,并分析连接的基因,对 32 个 RNA-seq 样本进行了共识 WGCNA。该分析确定了 14 个不同的模块。我们证明,在每个数据集的感染中,洋红色模块与感染呈显著相关。此外,我们发现两个数据集的蓝色和青色模块与感染呈相反的相关系数。然而,两个数据集之间的相关系数和 -值略有不同。内皮细胞基因的枢纽功能分析揭示了 TNF、AGE-RAGE、MAPK 和 NF-κB 信号的富集。另一方面,上皮细胞中富集了糖酵解、丙酮酸代谢、氨基酸、果糖、甘露糖和维生素 B6 代谢。然而,线粒体自噬、坏死性凋亡、凋亡过程和缺氧在内皮细胞和上皮细胞中均有富集。使用 STRING 和 CytoHubba 进行蛋白质-蛋白质相互作用分析显示,在内皮细胞中, 、 、 、 和 是内皮细胞的枢纽基因,而在上皮细胞中, 、 、 、 和 基因被鉴定出来。了解这些异同可能为感染的发病机制以及新的治疗靶点和干预策略的开发提供新的见解。

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