Ty -jour t1 -miR -184通过靶向发育中的肺JF中的细胞死亡和血管生成信号通路来介导高氧诱导的损伤 - 欧洲呼吸杂志au -sandhu，karmyodh au -das，pragnya au -aghai，Zubair H. au -Anersson，Sture au -pryhuber，Gloria au -bhandari -bhandari，vineet Y1- 2020/01/01/01 UR-01 UR- http:///www.qdcxjkg.com/content/early/2020/07/30/13993003.01789-2019.Abstract N2- microRNAS（miRS）（miRS）通过中断肺泡和血管化而破坏正常的肺发育和功能，从而导致支气管肺增生性营养不良（BPD）的发育。在这里，我们报告说，miR-184在发育中的肺中以异常肺泡化和肺血管生成为特征的BPD表型中具有关键作用。我们观察到MiR-184在BPD临床标本中的表达增加：气管抽吸（TA），具有BPD的人类新生儿肺以及暴露于高氧的胎儿人类肺II型肺泡上皮细胞（TIIAEC）。与此相一致，我们还检测到整个肺中的miR-184-3p表达，在高氧诱导的实验性BPD小鼠的肺新鲜分离的TIIAEC中，以及暴露于高氧的胎儿小鼠中。我们证明了miR-184-3p的过表达加剧了BPD肺表型，而miR-184-3p表达的下调可以改善BPD表型并改善了呼吸功能。我们确定了miR-184特定靶标：血小板衍生的生长因子-Beta（PDGF-β）和GATA 2（FOG2）的朋友，也称为锌指蛋白家族成员（ZFPM2），并表明它们与肺部有很严格有关牙槽化和血管生成。使用基于细胞的荧光素酶分析，miR-184-3p表达的下调和miR-184-3p的基因敲低目标在肺TIIAEC和内皮细胞中PDGF-β和FOG2的基因敲低，我们从机械上表明，抑制miR-184-3p表达可改善miR-184-3p的表达 pulmonary alveolarization by regulating PDGF-β/AKT/Foxo3/Bax, Bcl2 signalling and enhances angiogenesis by Fog2/VEGF-A/Angiopoietin-1/2 pathway. Collectively, these data suggest that the use of miR-184-3p specific inhibitors may act as novel therapeutic interventions to control the adverse effects of hyperoxia on lung development and function.FootnotesSince the online publication of this early view article on 26 May 2020, the editors have been made aware of potential issues with some of the images used. This note has been added to make readers aware that this issue is currently being investigated by the editors and the authors. This note will be removed and a correction published, if found necessary by the investigation. The article was updated with this note and republished on 4 August, 2020.This 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. Shah has nothing to disclose.Conflict of interest: Dr. Sandhu has nothing to disclose.Conflict of interest: Dr. Das has nothing to disclose.Conflict of interest: Dr. Aghai has nothing to disclose.Conflict of interest: Dr. Andersson has nothing to disclose.Conflict of interest: Dr. Pryhuber has nothing to disclose.Conflict of interest: Dr. Bhandari has nothing to disclose. ER -