PT-期刊文章Au -declercq，Mathias au -de Zeeuw，Pauline au -Conchinha，Nadine V.Au -Geldhof -Geldhof，Vincent Au -Ramalho -Anabela S. au -garcía -garcía -caballero，Melissa au -brepoels，Brepoels，katleen au- Ensincinck，katleen au-Marjolein au -Carlon，Marianne S.Au -Bird，Matthew J.Au -Vinckier，Stefan au -Proesmans，Marijke au -Vermeulen，FrançoisAu -Dupont，Lieven au -Ghesquière，Ghesquière，Bart auu -dewerchin，Miekeke au -carmeliel，peterAU - Cassiman, David AU - Treps, Lucas AU - Eelen, Guy AU - Witters, Peter TI - Transcriptomic analysis of CFTR-impaired endothelial cells reveals a pro-inflammatory phenotype AID - 10.1183/13993003.00261-2020 DP - 2021 Apr 01 TA -European Respiratory Journal PG - 2000261 VI - 57 IP - 4 4099 - //www.qdcxjkg.com/content/57/4/2000261.short 4100 - //www.qdcxjkg.com/content/57/4/2000261.Full SO -EUR RESTIR J2021 APR 01;57 AB-囊性纤维化（CF）是一种威胁生命的疾病，其特征是肺部粘膜固定和病原体清除率降低，并且夸张的炎症反应导致肺部造成肺部损伤。CF是由编码氯化物通道的囊性纤维化跨膜电导调节剂（CFTR）基因的双期纤维化跨膜电导调节剂（CFTR）基因引起的。CFTR在内皮细胞（ECS）中表达，CF患者已经报道了EC功能障碍，但是ECS中该离子通道在CF疾病进展方面的作用很差。封锁（通过CFTR抑制剂CFTRINH-172）在人类EC中表征CFTR损伤时的变化。在CFTR-KNOCKOUT小鼠和CF患者衍生的EC中，在体外和体内进一步验证了关键发现。CFTR损伤模型表明，EC的增殖，迁移和自噬被下调。但是，值得注意的是，有缺陷的CFTR功能导致EC激活和内皮的持续促炎状态，白细胞粘附增加。 Further validation in CFTR-knockout mice revealed enhanced leukocyte extravasation in lung and liver parenchyma associated with increased levels of EC activation markers. In addition, CF patient-derived ECs displayed increased EC activation markers and leukocyte adhesion, which was partially rescued by the CFTR modulators VX-770 and VX-809.Our integrated analysis thus suggests that ECs are no innocent bystanders in CF pathology, but rather may contribute to the exaggerated inflammatory phenotype, raising the question of whether normalisation of vascular inflammation might be a novel therapeutic strategy to ameliorate the disease severity of CF.CFTR-impaired endothelial cells have a pro-inflammatory phenotype that can attract and reinforce leukocyte extravasation. Endothelial cells possibly contribute to the excessive inflammatory phenotype observed in cystic fibrosis. https://bit.ly/2GRijq8