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Fig. 7 | Journal of Neuroinflammation

Fig. 7

From: Recombinant human plasma gelsolin reverses increased permeability of the blood–brain barrier induced by the spike protein of the SARS-CoV-2 virus

Fig. 7

Plasma gelsolin (pGSN) inhibits NF-κB activation by the SARS-CoV-2 Spike protein S1 subunit in hCMEC/D3 cells. Panel A shows a Log2 fold change heat map for genes involved in VEGF signaling and activation of blood–brain barrier endothelial cells upon 6 h stimulation with pGSN [250 µg/mL], S1 [10 nM] and S1 [10 nM] + pGSN [250 µg/mL]. Log2 fold change was calculated based on delta Ct values compared to the control samples. Warmer colors imply increased expression, while cold reflects decreased expression. The assay was performed twice in quadruplicate; data within frames shows Log2FC for every tested gene. Panel B shows the schematic representation of signaling pathways triggered by the SARS-CoV-2 Spike protein S1 subunit in hCMEC/D3 cells. (1) Spike protein interacts with the given receptor on a cell membrane, which (2) activates the catalytic effect of PI3K on PIP2, (3) enzymatically transforming it to PIP3, which is possibly inhibited by plasma gelsolin given its direct binding to PIP2. (4) PIP3 binds to AKT, promoting its phosphorylation and activation. (5, 6) Activated AKT regulates transcriptional activity of MAPK kinases and NF-κB by inducing phosphorylation and degradation of inhibitor of κB (IκB). (7) MAPK initiates the downstream induction of NF-κB and its translocation (8) to the nucleus. (9, 10) NF-κB, after activation, triggers the transcription of various genes and thereby regulates inflammation

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