Bioinformatics analyses reveal cell-barrier junction modulations in lung epithelial cells on SARS-CoV-2 infection
Bioinformatics analyses reveal cell-barrier junction modulations in lung epithelial cells on SARS-CoV-2 infection
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DOI：
10.1080/21688370.2021.2000300
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发表时间：
2021-11-07
期刊：
影响因子：
3.1
通讯作者：
Somanath, Payaningal R.
中科院分区：
文献类型：
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作者：
Adil, Mir S.;Khulood, Daulat;Somanath, Payaningal R.
细胞连接维持血液-组织屏障，以保持血管和组织的完整性。据报道，病毒感染会调节细胞间的连接，以促进它们的入侵。然而，关于新冠肺炎感染对细胞连接和细胞骨架蛋白基因表达的影响的信息有限。利用基因表达总览和反应组数据库，我们分析了人肺A549、NHBE和CALU-3细胞在SARS-CoV-2感染后细胞连接和细胞骨架蛋白表达的变化。分析发现，在CoV-2感染的CALU-3细胞中，A549基因发生了3660个基因的变化，NHBE基因发生了100个基因的变化，592个基因发生了变化。有趣的是，EGOT(9.8、3和8.3倍；p<；0.05)和CSF3(4.3、33和56.3倍；p<；0.05)是所有三种细胞系(分别为A549、NHBE和CALU-3)中仅有的两个显著升高的基因。另一方面，与细胞连接和细胞骨架相关的39个基因在肺细胞中被调控，其中DLL1在所有细胞中都发生了变化。分析中还发现了与细胞连接和细胞骨架基因相关的几个miRNAs的变化。此外，参与疾病病理的基质金属蛋白酶，包括基质金属蛋白酶-3、-9和-12，在冠状病毒-2感染中的表达升高(p<；0.05)。研究结果强调了细胞连接和细胞骨架基因在新冠肺炎中的不可或缺的作用，暗示了它们的治疗潜力。我们的分析还发现了一个独特的EGOT基因，以前没有发现与新冠肺炎有关。对这些新发现的基因和miRNAs的进一步研究可能会促进新冠肺炎的发病机制和治疗方面的进展。
Cell junctions maintain the blood-tissue barriers to preserve vascular and tissue integrity. Viral infections reportedly modulate cell-cell junctions to facilitate their invasion. However, information on the effect of COVID-19 infection on the gene expression of cell junction and cytoskeletal proteins is limited. Using the Gene Expression Omnibus and Reactome databases, we analyzed the data on human lung A549, NHBE, and Calu-3 cells for the expression changes in cell junction and cytoskeletal proteins by SARS-CoV-2 (CoV-2) infection. The analysis revealed changes in 3,660 genes in A549, 100 genes in NHBE, and 592 genes in Calu-3 cells with CoV-2 infection. Interestingly, EGOT (9.8-, 3- and 8.3-fold; p < .05) and CSF3 (4.3-, 33- and 56.3-fold; p < .05) were the only two genes significantly elevated in all three cell lines (A549, NHBE and Calu-3, respectively). On the other hand, 39 genes related to cell junctions and cytoskeleton were modulated in lung cells, with DLL1 demonstrating alterations in all cells. Alterations were also seen in several miRNAs associated with the cell junction and cytoskeleton genes modulated in the analysis. Further, matrix metalloproteinases involved in disease pathologies, including MMP-3, -9, and -12 demonstrated elevated expression on CoV-2 infection (p < .05). The study findings emphasize the integral role of cell junction and cytoskeletal genes in COVID-19, suggesting their therapeutic potential. Our analysis also identified a distinct EGOT gene that has not been previously implicated in COVID-19. Further studies on these newly identified genes and miRNAs could lead to advances in the pathogenesis and therapeutics of COVID-19.