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. 2020 Jul 14;11:526. doi: 10.3389/fendo.2020.00526

Figure 1.

Figure 1

Schematic representation of the activation of RAGE axis in Sars-Cov-2 infected cells in DM patients. Hyperglycemia enhances the production of RAGE ligands that prompt viral replication and increase RAGE signaling activation thus contributing to NRLP3 inflammasome priming and activation. Cytokine production and HMGB1 passive secretion contribute to dysregulated immune cell responses like M1 macrophages polarization, NETs formation, altered Th17 lymphocytes differentiation, thus paving the way for the cytokine storm. The preexisting endothelial dysfunction of DM patients and the ability of HMGB1 to activate platelets contribute to the pathogenesis of lung-centric and eventually multiorgan intravascular coagulopathy. Side panel shows druggable targets of molecular and clinical intervention. Targeting the RAGE pathway may represent a useful and feasible strategy for controlling severe ARDS and coagulopathy, particularly in DM patients. DPP4, Dipeptidyl-peptidase 4; SGLT2, Sodium-Glucose Cotransporter 2; LMWH, Low Molecular Weights Heparins.