Endothelial hyper-permeability is the hallmark of Acute Respiratory Distress Syndrome (ARDS). Laborious efforts in the investigation of the molecular pathways involved in the regulation of the vascular barrier, shall reveal novel therapeutic targets towards that respiratory disorder. Herein we investigate in vitro the effects of the alpha-1,2- mannosidase 1 inhibitor Kifunensine (KIF) and brefeldin A (BFA) in the LPS-induced endothelial breakdown. Our results suggest that BFA opposes the deteriorating effects of KIF (UPR suppressor) towards the lung microvasculature. Since KIF is an unfolded protein response (UPR) suppressor, and brefeldin A is a UPR inducer, we suggest that a carefully devised UPR manipulation may deliver novel therapeutic avenues in diseases related to endothelial barrier dysfunction (e.g. ARDS, sepsis).

中文翻译：

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Brefeldin A 和 Kifunensine 调节 LPS 诱导的人和牛细胞肺内皮通透性过高

内皮高渗透性是急性呼吸窘迫综合征 (ARDS) 的标志。在研究参与调节血管屏障的分子途径方面的艰苦努力将揭示针对该呼吸系统疾病的新治疗靶点。在这里，我们在体外研究了 alpha-1,2-甘露糖苷酶 1 抑制剂 Kifunensine (KIF) 和 brefeldin A (BFA) 在 LPS 诱导的内皮分解中的作用。我们的研究结果表明，BFA 反对 KIF（UPR 抑制因子）对肺微血管系统的恶化作用。由于 KIF 是一种未折叠蛋白反应 (UPR) 抑制剂，而布雷非菌素 A 是一种 UPR 诱导剂，我们建议精心设计的 UPR 操作可能会为与内皮屏障功能障碍相关的疾病（例如 ARDS、败血症）提供新的治疗途径。