肺血管内皮通透性增加为ARDS的特征性表现。肺内皮细胞SPNS2（Spinster Homolog 2）释放的S1P可增强肺内皮屏障，而其在ARDS中的作用尚不明确。我们前期发现SPNS2可磷酸化位点（S-266）变异降低其S1P转运活性。本课题将在细胞/动物层面探索SPNS2磷酸化对S1P转运活性、肺内皮屏障、以及ARDS的影响。并在ARDS病人中筛查SPNS2磷酸化位点基因型，测定血浆及肺泡灌洗液(BAL)中S1P水平，获取肺内皮屏障指标（Picco导管：肺血管通透性、血管外肺水指数），计算肺损伤评分。综合评估SPNS2磷酸化如何对血浆/BAL中S1P水平、肺血管通透性、以及ARDS产生影响。探讨血浆/BAL中S1P水平作为ARDS病人肺损伤的生物学标志物可能。本研究将从分子生物学和临床研究深入揭示SPNS2磷酸化对ARDS的影响，加深对ARDS的理解，为新治疗方案的开发打下理论基础。

Increased pulmonary vascular permeability is a hallmark of ARDS. Endogenous Spingosine-1-phosphate (S1P) released through SPNS2 by pulmonary endothelial cells has endothelial barrier protective properties. However, it is yet unknown how SPNS2 affects the recovery of ARDS. Our preliminary data shows that SPNS2 phosphorylation site (S-266) mutation decreased its S1P transportation activity. In this project, we will determine, at cellular and animal levels, how SPNS2 phosphorylation impacts S1P transportation, endothelial barrier function, as well as the recovery of ARDS. In the meantime, we will genotype SPNS2 in ARDS patients, measure S1P levels in blood and bronchoalveolar lavage (BAL) fluid, obtain clinical lung endothelial barrier function indexes (PVPI & EVLW measured by PiCCO catheter), and calculate the lung injury score (Murray score). We will subsequently determine how SPNS2 phosphorylation affect blood/BAL S1P levels, lung endothelial barrier function indexes, and the severity of lung injury in ARDS. In addition, we will evaluate the possibility of using S1P levels in blood/BAL as a biomarker for lung injury in ARDS patients. This study will determine how SPNS2 phosphorylation impacts ARDS at benchside and clinical levels, improve our understanding of ARDS, and provide ground knowledge for early interventions of the disease.