Upregulation of the MAP2K4 gene triggers endothelial-mesenchymal transition in COVID-19.

Abstract

Background: SARS-CoV-2 infection is marked by an excessive inflammatory response, leading to elevated production of pro-inflammatory cytokines through activation of intracellular pathways like mitogen-activated protein kinase (MAPK). Viruses can use the MAPK signaling pathway to their advantage, but the relationship of this pathway to the severe SARS-CoV-2 period has not been fully elucidated. MAP2K4 is involved in the MAPK signaling pathway and affects cellular processes such as cell-cell junction, cell proliferation, differentiation and apoptosis.

Methods and results: In this study, we sought to determine the associated biomarkers that are involved in the MAP2K4 pathway and elucidate its possible roles in terms of some clinical features associated with COVID-19. We evaluated the expressions of MAP2K4, SNAI1, SLUG, ZEB1 and E-Cadherin. For this purpose, we prospectively recruited 66 individuals, 39 of whom were women and had a mean age of 65 years. The results revealed that MAP2K4 upregulation increased SNAI1 gene expression level whereas E- Cadherin level was decreased in SARS-CoV-2 positive participants. In addition, negative correlations were determined with PLT, Lymphocyte and CKMB and E- Cadherin levels in positive participants. We also observed a negative correlation between the MAP2K4 and AST, and a positive correlation between SLUG and BUN, ZEB1 and CK.

Conclusions: We conclude that SARS-CoV-2 infection triggers fibrosis by increasing MAP2K4 regulation. Additionally, this is the first study to demonstrate the possible contribution of MAP2K4 in influencing COVID-19 clinical features, which may be relevant for identifying COVID-19 positive participants with severe complications.