Sphingosine-1-phosphate receptor-1 (S1PR1), a G-protein coupled receptor that is expressed in endothelium and activated upon ligation by the bioactive lipid sphingosine-1-phosphate (S1P), is an important vascular-barrier protective mechanism at the level of adherens junctions (AJ). Loss of endothelial barrier function is a central factor in the pathogenesis of various inflammatory conditions characterized by protein-rich lung edema formation, such as acute respiratory distress syndrome (ARDS). While several S1PR1 agonists are available, the challenge of arresting the progression of protein-rich edema formation remains to be met. In this review, we discuss the role of S1PRs, especially S1PR1, in regulating endothelial barrier function. We review recent findings showing that replenishment of the pool of cell-surface S1PR1 may be crucial to the effectiveness of S1P in repairing the endothelial barrier. In this context, we discuss the S1P generating machinery and mechanisms that regulate S1PR1 at the cell surface and their impact on endothelial barrier function.

1-磷酸鞘氨醇受体-1 (S1PR1) 是一种在内皮细胞中表达的 G 蛋白偶联受体，通过生物活性脂质 1-磷酸鞘氨醇 (S1P) 连接后被激活，是重要的血管屏障保护机制。粘附连接水平（AJ）。内皮屏障功能丧失是各种炎症性疾病（例如急性呼吸窘迫综合征（ARDS））发病机制的核心因素，这些炎症性疾病以富含蛋白质的肺水肿形成为特征。虽然有几种 S1PR1 激动剂可用，但阻止富含蛋白质的水肿形成进展的挑战仍有待解决。在这篇综述中，我们讨论了 S1PR，特别是 S1PR1，在调节内皮屏障功能中的作用。我们回顾了最近的研究结果，表明细胞表面 S1PR1 库的补充可能对于 S1P 修复内皮屏障的有效性至关重要。在此背景下，我们讨论了 S1P 生成机制和调节细胞表面 S1PR1 的机制及其对内皮屏障功能的影响。