Regeneration of the pulmonary vascular endothelium after viral pneumonia requires COUP-TF2.
Sci Adv
; 6(48)2020 11.
Article
in English
| MEDLINE | ID: covidwho-1388431
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Regeneration
/
Endothelium, Vascular
/
Orthomyxoviridae Infections
/
Endothelial Cells
/
COUP Transcription Factor II
/
Influenza A Virus, H1N1 Subtype
/
Lung
Type of study:
Prognostic study
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Year:
2020
Document Type:
Article
Affiliation country:
SCIADV.ABC4493
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