Bioinformatics analyses reveal cell-barrier junction modulations in lung epithelial cells on SARS-CoV-2 infection.

Abstract

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.