Fig. 6. Schematic diagram of signal transduction pathways involved in Ang II-induced endothelial hyperpermeability via AT1R/RAGE/mDia1/Src/β-catenin/VE-cadherin.

a As Ang II binds to and stimulates AT1R, the expression and secretion of HMGB1 can be increased by NF-κB activation. NF-κB-mediated expression of proinflammatory molecules, including RAGE itself, can occur. HMGB1 binds to RAGE, which can induce RAGE-mediated activation of Src/β-catenin/VE-cadherin via mDia1. b Blockade of RAGE activation by sRAGE attenuates the Ang II-induced increase in endothelial hyperpermeability by inhibiting RAGE-mediated signaling pathways