TY -的T1 CFTR-impaired内皮细胞转录组分析揭示了一个炎性表型JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.00261 -2020欧元SP - 2000261 AU Declercq Mathias AU -德齐乌波林盟——塞·伐斯冈萨雷斯Conchinha他Nadine盟——Geldhof文森特盟——RamalhoAnabela s . AU - Garcia-Caballero梅丽莎盟——Brepoels Katleen盟——Ensinck Marjolein AU - Carlon,玛丽安美国非盟-鸟,马修·j . AU - Vinckier Stefan盟——Proesmans Marijke AU - Vermeulen,弗朗索瓦AU -杜邦,列文AU -盖斯基埃,巴特盟——Dewerchin Mieke盟——Carmeliet彼得盟——Cassiman大卫盟——Treps卢卡斯盟——Eelen人非盟-喋喋不休,彼得Y1 - 2020/01/01 UR - //www.qdcxjkg.com/content/early/2020/10/08/13993003.00261 2020. -抽象N2 -囊性纤维化(CF)是一种危及生命的疾病的特点是减少肺黏膜纤毛的清除病原体,和一个夸张的炎症反应导致进行性肺损伤。CF是由囊性纤维化跨膜传导调节基因(CFTR)的双等位基因致病性变异引起的，CFTR基因编码一个氯离子通道。CFTR在内皮细胞(ECs)中表达，CF患者EC功能障碍已被报道，但该离子通道在CF疾病进展中的作用尚不清楚。我们在人类ECs中CFTR沉默和阻断(通过CFTR抑制剂CFTRinh-(172))的互补模型中使用了一种无偏倚RNA测序方法，以表征CFTR损伤后的变化。关键发现在体外、体内CFTR敲除小鼠和体外CF患者来源的ECs中得到进一步验证。两种CFTR损伤模型均显示EC增殖、迁移和自噬下调。值得注意的是，CFTR功能缺陷导致EC激活和内皮持续的促炎状态，白细胞黏附增加。对CFTR敲除小鼠的进一步验证表明，肺和肝实质白细胞外渗的增强与EC激活标志物水平的升高有关。此外，CF患者来源的ECs显示EC激活标志物和白细胞粘附增加，使用CFTR调节剂VX770-VX809可部分挽救这些情况。因此，我们的综合分析表明，ECs在CF病理中并不是无辜的旁观者，而是可能有助于夸大的炎症表型， 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. ER -