Dilek Yilmaz’s research while affiliated with Yozgat State Hospital and other places

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.

SARS-CoV-2 penetrates human cells via its spike protein, which mainly interacts with ACE2 receptors, triggering viral replication and an exacerbated immune response characterized by a cytokine storm. Vimentin III, an intermediate filament protein predominantly found in mesenchymal cells, has garnered considerable attention in recent research due to its multifaceted biological roles and significance in the endothelial-mesenchymal transition (EndMT) during various fibrotic processes. However, the pathophysiological mechanisms linking vimentin to SARS-CoV-2 remain incompletely elucidated. In this study, we determined the expression profiles of vimentin in three cohorts: patients admitted to the intensive care unit with SARS-CoV-2 infection, individuals in the 6–12 month convalescent phase post-infection and COVID-19 negative controls. Our objective was to assess the association between peripheral blood biomarkers implicated in endothelial dysfunction and genes related to fibrosis. Serum levels of vimentin and N-cadherin were determined by ELISA, while vimentin gene expression was determined by qRT-PCR. In addition, we examined the correlation between clinical parameters and serum levels of vimentin and N-cadherin in severe COVID-19 patients and healthy counterparts. Our findings revealed elevated serum vimentin levels and increased gene expression in severe COVID-19 patients compared to healthy controls. Conversely, serum N-cadherin levels were diminished in both acute and convalescent stages of severe COVID-19 relative to healthy individuals. Notably, associations were observed between C-reactive protein, lactate dehydrogenase, lymphocyte count and vimentin levels in severe COVID-19 patients, indicative of endothelial dysfunction. Furthermore, our study identified vimentin and N-cadherin as potential diagnostic markers via ROC analysis. Overall, delineating the dysregulation of vimentin and N-cadherin due to SARS-CoV-2 infection in disease pathogenesis and tissue homeostasis offers novel insights for clinical management and targeted therapeutic interventions.