Fig. 8.

A schematic of the role of the P2Y₂ receptor in shear stress-mediated cell alignment, formation of ASF and wound closure. It is well established that extracellular nucleotides activate P2Y₂ receptors and increase the intracellular calcium concentration via Gαq, phospholipase C (PLC)-β, and inositol triphosphate (IP₃) [66, 67]. In this study, under shear stress conditions, we show P2Y₂ receptors (1) phosphorylate AKT and eNOS; (2) modulate shear stress-induced endothelial cytoskeletal alterations via their integrin-binding RGD domain through the activation of FAK and cofilin-1; and (3) promote wound repair in HUVECs. Additionally, in support of this model, previous studies have demonstrated that activation of AKT regulates eNOS [68] and cofilin-1 activities [69]