％0刊杂志百分之一，Mathias％A de Zeeuw，Pauline％A vasconcelos conchinha，Nadine％Geldhof，Vincent％a Ramalho，Anabela s.％agarcía-caballero，melissa％brepoels，Katleen％a ensinck，marjolein％A Carlon，Marianne S.％A Bird，Matthew J.％A Vinckier，Stefan％A Proesmans，Marijke％A vermeulen，François％杜邦，Lieven％AGhesquière，Bart％A Dewerchin，Mieke％A Carmeliet，Peter％CASSIMAN，David％A TREPS，LUCAS％AEELEN，GUY％A WITTERS，CFTR受损内皮细胞的PETER％T转录组分析揭示了促炎表型％D 2020％R 10.1183 / 13993003.00261-2020％J欧洲呼吸杂志％P 2000261％X囊性纤维化（CF）是一种危及生命的疾病，其特征在于肺粘膜蛋白碳和病原体间隙降低，夸张的炎症反应导致进步肺部损伤。CF是由编码氯通道的囊性纤维化跨膜电导调节剂（CFTR）基因的双等等位基因致病变体引起的。CFTR在内皮细胞（ECS）和EC功能障碍中表达，CF患者报告了EC功能障碍，但在CF疾病进展中的这种离子通道的作用很差。我们在CFTR沉默和封锁的互补模型中使用了无偏的RNA测序方法（通过CFTR抑制剂CFTRINH-（172））在人EC中，以表征CFTR损伤的变化。在体外进一步验证了主要发现，在CFTR敲除小鼠中的体内，CF患者衍生的ECS中的exvivo。CFTR障碍的模型表明EC增殖，迁移和自噬下调了。尽管如此，有缺陷的CFTR功能导致EC激活和内皮的持续性促炎状态，随着白细胞粘附增加。CFTR敲除小鼠的进一步验证显示肺和肝实质增强的白细胞外渗与EC活化标志物增加相关的肺和肝实质。此外，CF患者衍生的EC显示出增加的EC活化标记和白细胞粘附，通过使用CFTR调制器VX770-VX809部分抵押。因此，综合分析表明，EC在CF病理学中没有无辜的旁观者，而是可能有助于 exaggerated inflammatory phenotype, raising the question whether normalisation of vascular inflammation might be a novel therapeutic strategy to ameliorate the disease severity of CF.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Yan reports grants from National Institutes of Health, during the conduct of the study;.Conflict of interest: Dr. Declercq has nothing to disclose.Conflict of interest: Dr. de Zeeuw has nothing to disclose.Conflict of interest: Nadine Conchinha has nothing to disclose.Conflict of interest: Dr. Geldhof has nothing to disclose.Conflict of interest: Dr. Ramalho has nothing to disclose.Conflict of interest: Dr. García-Caballero has nothing to disclose.Conflict of interest: Dr. Brepoels has nothing to disclose.Conflict of interest: Dr. Ensinck has nothing to disclose.Conflict of interest: Dr. Carlon has nothing to disclose.Conflict of interest: Dr. Bird has nothing to disclose.Conflict of interest: Dr. Vinckier has nothing to disclose.Conflict of interest: Dr. Proesmans has nothing to disclose.Conflict of interest: Dr. Vermeulen has nothing to disclose.Conflict of interest: Dr. Dupont has nothing to disclose.Conflict of interest: Dr. Ghesquière has nothing to disclose.Conflict of interest: Dr. Eelen has nothing to disclose.Conflict of interest: Dr. Dewerchin has nothing to disclose.Conflict of interest: Dr. Carmeliet has nothing to disclose.Conflict of interest: Dr. Cassiman has nothing to disclose.Conflict of interest: Dr. Treps has nothing to disclose.Conflict of interest: Dr. Witters has nothing to disclose. %U //www.qdcxjkg.com/content/erj/early/2020/10/08/13993003.00261-2020.full.pdf