IndraLab

"The process of platelet interaction with the vessel wall and subendothelial matrix is accomplished through the involvement of many platelet receptors and their corresponding ligands ( xref ).[ xref ] Major platelet surface receptors include the GPIb-IX-V complex, GPVI, integrins αIIbβ3 (also known as GPIIbIIIa), α2β1, α5β1, α6β1, thrombin receptors PAR1 and PAR4 (protease activated receptors), ADP receptors (P2Y1, P2Y12 and P2X1) and thromboxane A2 receptors (TP).[ xref ] Platelet adhesion: Platelet-vessel wall interaction, the tethering and adhesion of platelets to the injured site, is primarily mediated by platelet surface GPIbα receptor in GPIb-IX-V complex which binds to the A1 domain of von Willebrand factor (VWF) immobilized on collagen upon vascular injury, particularly at high shear stress.[ xref ] Subsequent stable platelet adhesion is further mediated by other integrin ligands with their corresponding ligands such as integrin αIIbβ3 bound to fibronectin and fibrinogen/fibrin, α5β1 to fibronectin or collagen, and α2β1 to collagen.[ xref ] Platelet activation : Following initial tethering and adhesion of circulating resting platelets at the site of vascular injury, platelets rapidly undergo a well-defined signaling cascade (Ca 2+ influx, degranulation, phosphatidylserine exposure, etc.) that leads to platelet shape change facilitating further platelet activation and platelet granule release.[ xref ] Platelet α-granule (P-selectin[ xref ], VWF[ xref ], fibrinogen (Fg)[ xref ], fibronectin[ xref ], vitronectin[ xref ], multimerin[ xref ], platelet factor 4[ xref ], and many other proteins) and dense granule (adenosine di-phosphate (ADP), polyphosphates and other) contents are secreted and, in turn, amplify the activation process of integrin αIIbβ3 inside-out signaling, leading to further platelet aggregation.[ xref ] GPIba-VWF interaction is also shown to play an important role in platelet adhesion at low shear conditions.[ xref ] Platelet aggregation: Activation of platelets is a critical step for aggregation."

"For the present question of the binding of α5β1 with PHSRN and RGD, inhibition studies here and in a previous report have shown that both PHSRN and RGD are capable of competitively binding to this integrin to block cell adhesion to substrates presenting either peptide.( xref ) Another study similarly showed that both RGD and a PHSRN-containing peptide could inhibit the interaction between the αIIbβ3 integrin and FN.( xref ) These reports, taken together with the adhesion data presented in this current study, support a model where PHSRN and RGD competitively bind to the same site in the integrin receptor to mediate cell adhesion."