2. Academic Validation
  3. Regeneration of the pulmonary vascular endothelium after viral pneumonia requires COUP-TF2

Regeneration of the pulmonary vascular endothelium after viral pneumonia requires COUP-TF2

  • Sci Adv. 2020 Nov 25;6(48):eabc4493. 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 5 2 6
Affiliations

Affiliations

  • 1 Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 2 Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 3 Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
  • 4 Pulmonary, Allergy, and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 5 Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. [email protected].
  • 6 Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
PMID: 33239293 DOI: 10.1126/sciadv.abc4493
Abstract

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.

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