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• W2912509762 abstract "Abstract The neuropilin-1 (NRP1)-MET signaling axis regulates the motility of individual endothelial cells (ECs). It is unknown how this signaling pathway affects the endothelial barrier in coherent ECs forming a tight monolayer. We hypothesized that it is involved both in modulation of the endothelial barrier and in EC activation. To investigate the role of NRP1–MET signaling in inflammatory processes (e.g., systemic inflammatory response syndrome [SIRS] or snakebite-induced SIRS-like conditions), we employed the C-type lectin-related protein rhodocetin-αβ (RCαβ) as a specific trigger of this signal axis in ECs in vitro. In coherent HUVECs, RCαβ reinforced the actin cytoskeleton and increased cell stiffness, thus favoring vascular endothelial cadherin–mediated transmission of intercellular forces. Increased cell stiffness was associated with enhanced activation of RhoA and nuclear translocation of NF-κB. Simultaneously, RCαβ-triggered signaling via the NRP1–MET axis increased EC monolayer permeability, induced transcription of proinflammatory genes such as ICAM-1 and, consequently, leukocyte tethering. The RCαβ-induced transcriptome differed from that induced by hepatocyte growth factor, although in both cases the same tyrosine kinase, MET, was involved. This was due to RCαβ-mediated recruitment of the MET coreceptor NRP1 and additional Rho-mediated activation of the actomyosin system. RCαβ induced similar transcriptional and cellular changes if external shear forces were applied. These data highlight the modulatory role of NRP1 as MET coreceptor, and they explain how some snake venoms induce SIRS-like conditions. Additionally, this study demonstrates that inflammatory activation of coherent ECs is triggered by converging signals that are induced by NRP1–MET signaling and influenced by intercellular forces." @default.
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• W2912509762 date "2019-03-01" @default.
• W2912509762 modified "2023-09-30" @default.
• W2912509762 title "Signals of the Neuropilin-1–MET Axis and Cues of Mechanical Force Exertion Converge to Elicit Inflammatory Activation in Coherent Endothelial Cells" @default.
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• W2912509762 doi "https://doi.org/10.4049/jimmunol.1801346" @default.
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