RAGE Plays a Role in LPS-Induced NF-κB Activation and Endothelial Hyperpermeability
AbstractEndothelial functional dysregulation and barrier disruption contribute to the initiation and development of sepsis. The receptor for advanced glycation end products (RAGE) has been demonstrated to be involved in the pathogenesis of sepsis. The present study aimed to investigate the role of RAGE in lipopolysaccharide (LPS)-induced nuclear factor-κB (NF-κB) activation in endothelial cells and the consequent endothelial hyperpermeability. LPS-induced upregulation of RAGE protein expression in human umbilical vein endothelial cells (HUVECs) was detected by western blotting. Activation of NF-κB was revealed using western blotting and immunofluorescent staining. LPS-elicited endothelial hyperpermeability was explored by transendothelial electrical resistance (TER) assay and endothelial monolayer permeability assay. The blocking antibody specific to RAGE was used to confirm the role of RAGE in LPS-mediated NF-κB activation and endothelial barrier disruption. We found that LPS upregulated the protein expression of RAGE in a dose- and time-dependent manner in HUVECs. Moreover, LPS triggered a significant phosphorylation and degradation of IκBα, as well as NF-κB p65 nuclear translocation. Moreover, we observed a significant increase in endothelial permeability after LPS treatment. However, the RAGE blocking antibody attenuated LPS-evoked NF-κB activation and endothelial hyperpermeability. Our results suggest that RAGE plays an important role in LPS-induced NF-κB activation and endothelial barrier dysfunction. View Full-Text
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Wang, L.; Wu, J.; Guo, X.; Huang, X.; Huang, Q. RAGE Plays a Role in LPS-Induced NF-κB Activation and Endothelial Hyperpermeability. Sensors 2017, 17, 722.
Wang L, Wu J, Guo X, Huang X, Huang Q. RAGE Plays a Role in LPS-Induced NF-κB Activation and Endothelial Hyperpermeability. Sensors. 2017; 17(4):722.Chicago/Turabian Style
Wang, Liqun; Wu, Jie; Guo, Xiaohua; Huang, Xuliang; Huang, Qiaobing. 2017. "RAGE Plays a Role in LPS-Induced NF-κB Activation and Endothelial Hyperpermeability." Sensors 17, no. 4: 722.