PT - JOURNAL ARTICLE AU - Shah, Dilip AU - Sandhu, Karmyodh AU - Das, Pragnya AU - Aghai, Zubair H. AU - Andersson, Sture AU - Pryhuber, Gloria AU - Bhandari，Vineet TI - mir - 184介导hyperoxia-induced伤针对细胞死亡和血管生成信号通路在发展中肺援助- 10.1183/13993003.01789 -2019 DP - 2020年1月01 TA -欧洲呼吸杂志PG - 1901789 4100 - 4099 - //www.qdcxjkg.com/content/early/2020/07/30/13993003.01789 2019. -短//www.qdcxjkg.com/content/early/2020/07/30/13993003.01789-2019.full AB - MicroRNAs (miRs)已经被证明通过中断肺泡形成和血管形成导致支气管肺发育不良(BPD)的发展而破坏正常的肺发育和功能。在这里，我们报道了miR-184在BPD表型的诱导中起关键作用，其特征是发育中的肺中异常的肺泡形成和肺血管生成。我们观察到在BPD临床标本中miR-184的表达增加:气管吸出物(TA)、BPD新生儿肺和高氧暴露的胎儿人肺II型肺泡上皮细胞(TIIAECs)。与此相一致，我们还检测到全肺、高氧诱导的实验性BPD小鼠新鲜分离的tiiaec和高氧暴露的胎鼠肺tiiaec中miR-184-3p表达上调。我们发现，miR-184-3p的过表达加重了BPD肺表型，而下调miR-184-3p表达改善了BPD表型，并改善了呼吸功能。我们鉴定了miR-184的特定靶点:血小板衍生生长因子-β (Pdgf-β)和Gata 2的朋友(Fog2)，也被称为锌指蛋白家族成员(Zfpm2)，并表明它们在肺泡形成和血管生成中起关键作用。使用基于细胞的荧光素酶分析，下调miR-184-3p表达和基因敲低miR-184-3p在肺TIIAECs和内皮细胞中靶向Pdgf-β和Fog2，我们从机制上表明，抑制miR-184-3p表达通过调节Pdgf-β /AKT/Foxo3/Bax改善肺泡化。Bcl2通过Fog2/VEGF-A/Angiopoietin-1/2通路发出信号并增强血管生成。 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.