Spatially and Mechanistically Distinct S1P Receptor Subtypes have Opposing Effects on Pulmonary Epithelial and Endothelial Barriers

S1P modulates epithelial and endothelial barrier function. S1P induced S1P3 activation in alveolar epithelium results in increased permeability via tight junction opening and ZO-1 loss, likely through Rho activation. In contrast, activation of S1P1 receptor on endothelial cells activates Rac1 GTPase inducing downstream assembly and stabilization of cell-cell junctions with reorganization of actin cytoskeleton and VE-cadherin. G: G-protein; Green and orange circles: cell-cell junctions. Reprinted with permission. Copyright (2005) National Academy of Sciences, U.S.A.