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是由编码氯离子通道的囊性纤维化跨膜电导调节基因(CFTR)的双等位致病变异引起的。CFTR在内皮细胞(ECs)中表达，已报道在CF患者中EC功能障碍，但该离子通道在CF疾病进展中的作用尚不清楚。我们在CFTR沉默和阻断(由CFTR抑制剂CFTRinh-(172))的人类ec的互补模型中使用了无偏差的RNA测序方法来描述CFTR损伤后的变化。在CFTR敲除小鼠和CF患者源性ECs的体内外，关键发现得到了进一步的验证。两种CFTR损伤模型均显示EC增殖、迁移和自噬水平下调。值得注意的是，CFTR功能缺陷导致EC激活和内皮持续的促炎症状态，并增加白细胞粘附。在CFTR敲除小鼠中进一步验证发现肺和肝实质白细胞外渗增强与EC活化标志物水平增加相关。此外，CF患者来源的ECs显示EC激活标记物和白细胞粘附增加，这部分可通过使用CFTR调节剂VX770-VX809得到挽救。因此，我们的综合分析表明，ec在CF病理中不是无辜的旁观者，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 -