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Regeneration of the pulmonary vascular endothelium after viral pneumonia requires COUP-TF2
Science Advances ( IF 11.7 ) Pub Date : 2020-11-25 , DOI: 10.1126/sciadv.abc4493
Gan Zhao 1, 2, 3 , Aaron I. Weiner 1, 2 , Katherine M. Neupauer 1 , Maria Fernanda de Mello Costa 1, 2 , Gargi Palashikar 1, 2 , Stephanie Adams-Tzivelekidis 1, 2 , Nilam S. Mangalmurti 4 , Andrew E. Vaughan 1, 2, 5
Affiliation  

Acute respiratory distress syndrome is associated with a robust inflammatory response that damages the vascular endothelium, impairing gas exchange. While restoration of microcapillaries is critical to avoid mortality, therapeutic targeting of this process requires a greater understanding of endothelial repair mechanisms. Here, we demonstrate that lung endothelium possesses substantial regenerative capacity and lineage tracing reveals that native endothelium is the source of vascular repair after influenza injury. Ablation of chicken ovalbumin upstream promoter–transcription factor 2 (COUP-TF2) (Nr2f2), a transcription factor implicated in developmental angiogenesis, reduced endothelial proliferation, exacerbating viral lung injury in vivo. In vitro, COUP-TF2 regulates proliferation and migration through activation of cyclin D1 and neuropilin 1. Upon influenza injury, nuclear factor κB suppresses COUP-TF2, but surviving endothelial cells ultimately reestablish vascular homeostasis dependent on restoration of COUP-TF2. Therefore, stabilization of COUP-TF2 may represent a therapeutic strategy to enhance recovery from pathogens, including H1N1 influenza and SARS-CoV-2.



中文翻译:

病毒性肺炎后肺血管内皮的再生需要COUP-TF2

急性呼吸窘迫综合征与强烈的炎症反应有关,后者会损害血管内皮,损害气体交换。尽管微毛细管的恢复对于避免死亡至关重要,但针对该过程的治疗目标需要对内皮修复机制有更深入的了解。在这里,我们证明了肺内皮具有实质性的再生能力,沿袭谱系揭示了天然内皮是流感损伤后血管修复的来源。鸡卵清蛋白上游启动子转录因子2(COUP-TF2)(Nr2f2)的消融是一种与发育性血管生成有关的转录因子,可减少内皮细胞的增殖,并在体内加剧病毒性肺损伤。在体外,COUP-TF2通过激活cyclin D1和neuropilin 1调节增殖和迁移。流感损伤后,核因子κB抑制COUP-TF2,但存活的内皮细胞最终会依赖于COUP-TF2的恢复而重建血管稳态。因此,稳定COUP-TF2可能代表增强从病原体(包括H1N1流感和SARS-CoV-2)中恢复的治疗策略。

更新日期:2020-11-25
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