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.