Sphingosine-1-Phosphate and Its Receptors: A Mutual Link between Blood Coagulation and Inflammation

Figure 2

Thrombin effects in endothelial cells involve S1P signaling. Activation of the classical thrombin receptor PAR-1 interrupts endothelial barrier integrity by induction of endothelial contraction through stimulation of G_12/13 subunit and Rho signalling pathway (left). Conversely, thrombin also induces expression of SphK1 and increases S1P generation. This involves PAR-1-induced signaling via activated protein C (APC) and the endothelial protein C receptor (EPCR). S1P in turn transactivates S1PR1 leading to -dependent activation of the Rac-1 signaling pathway. This effect improves endothelial integrity to counteract and limit thrombin-induced endothelial damage and vascular leakage (right).