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10.1126/sciadv.abc4493

http://scihub22266oqcxt.onion/10.1126/sciadv.abc4493
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33239293!7688336!33239293
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suck abstract from ncbi


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pmid33239293      Sci+Adv 2020 ; 6 (48): ä
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  • Regeneration of the pulmonary vascular endothelium after viral pneumonia requires COUP-TF2 #MMPMID33239293
  • Zhao G; Weiner AI; Neupauer KM; de Mello Costa MF; Palashikar G; Adams-Tzivelekidis S; Mangalmurti NS; Vaughan AE
  • Sci Adv 2020[Nov]; 6 (48): ä PMID33239293show ga
  • 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 kappaB 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.
  • |*Influenza A Virus, H1N1 Subtype[MESH]
  • |Animals[MESH]
  • |COUP Transcription Factor II/genetics/*metabolism[MESH]
  • |Cell Movement/genetics[MESH]
  • |Cell Proliferation/genetics[MESH]
  • |Disease Models, Animal[MESH]
  • |Endothelial Cells/*metabolism[MESH]
  • |Endothelium, Vascular/*metabolism[MESH]
  • |Female[MESH]
  • |Gene Knockout Techniques[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Lung/*cytology/*physiology[MESH]
  • |Male[MESH]
  • |Mice[MESH]
  • |Mice, Transgenic[MESH]
  • |Orthomyxoviridae Infections/*metabolism/virology[MESH]
  • |Regeneration/*genetics[MESH]


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