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

• DOI: 10.1126/sciadv.abc4493
• Publication Date: 2020-11-26T00:15:56Z
• Authors: Gan Zhao; Aaron I. Weiner; Katherine M. Neup...; Maria Fernanda de...; Gargi Palashikar; Stephanie Adams-T...; Nilam S. Mangalmurti; Andrew E. Vaughan
• Keywords: Male; 0301 basic medicine; Multidisciplinary; Endothelial Cells; Mice, Transgenic; Transfection; 3. Good health; COUP Transcription Factor II; Disease Models, Animal; Gene Knockout Techniques; Mice; 03 medical and health sciences; HEK293 Cells; Influenza A Virus, H1N1 Subtype; Orthomyxoviridae Infections; Cell Movement; 13. Climate action; Animals; Humans; Regeneration; Female; Endothelium, Vascular; Lung; Research Articles; Cell Proliferation

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