SPHK1 maintains endothelial barrier function and reanneals adherens junctions, thus hastens the recovery process.

Abstract Disruption of endothelial barrier is a crucial factor in the pathogenesis tissue inflammation, hallmark inflammatory diseases such as diabetes and atherosclerosis. Increased permeability occurs because loss cell–cell contacts disruption cell–extracellular matrix (ECM) adhesions. Vascular injury associated with activation coagulation cascade release thrombin, which increases by activating cell surface thrombin receptor. This increase typically followed recovery period ≈2 hours, during integrity restored. It has been surmised that signaling stimulates intrinsic repair mechanisms restore function. To validate our finding we determined function using state art Electric Cell-substrate Impedance Sensing (ECIS) mechanism, measure trans-endothelial electrical resistance (TEER) across monolayers TEER electrodes. Our data show 50mM complete reannealing adherens junction control cells. However, SPHK1 depleted cells showed significantly decrease disruption, failed recover completely compared to monolayer. Upon treatment S1P endothelia In conclusion, study for first time shows SPHK1-S1P-S1PR1 pathway emerging potential therapeutic target improving prevent coronary artery disease. CTRE Seed Grant Professor Nadeem Fazal, MD, PhD