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

Zhao, Gan; Weiner, Aaron I.; Neupauer, Katherine M.; Costa, Maria Fernanda de Mello; Palashikar, Gargi; Adams-Tzivelekidis, Stephanie; Mangalmurti, Nilam S.; Vaughan, Andrew E.

doi:10.1126/sciadv.abc4493

Cited by 36 publications

(23 citation statements)

References 88 publications

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“…The study revealed that ligand-dependent NRP-1 is associated with angiogenesis and the migration of endothelial cells, and is directly targeted by COUP-TF2. Therefore, it was indicated that therapy of pulmonary vascular endothelium damage caused, inter alia, by SARS-CoV-2, can be based on the stabilization of COUP-TF2, which has an impact on NRP-1 [49].…”

Section: Resultsmentioning

confidence: 99%

The Role of Neuropilin-1 (NRP-1) in SARS-CoV-2 Infection: Review

Gudowska-Sawczuk

Mroczko

2021

JCM

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovered in 2019, is responsible for the global coronavirus disease 19 (COVID-19) pandemic. The main protein that interacts with the host cell receptor is the Spike-1 (S1) subunit of the coronavirus. This subunit binds with receptors present on the host cell membrane. It has been identified from several studies that neuropilin-1 (NRP-1) is one of the co-receptors for SARS-CoV-2 entry. Therefore, in this review, we focus on the significance of NRP-1 in SARS-CoV-2 infection. MEDLINE/PubMed database was used for a search of available literature. In the current review, we report that NRP-1 plays many important functions, including angiogenesis, neuronal development, and the regulation of immune responses. Additionally, the presence of this glycoprotein on the host cell membrane significantly augments the infection and spread of SARS-CoV-2. Literature data suggest that NRP-1 facilitates entry of the virus into the central nervous system through the olfactory epithelium of the nasal cavity. Moreover, published findings show that interfering with VEGF-A/NRP-1 using NRP-1 inhibitors may produce an analgesic effect. The review describes an association between NRP-1, SARS-CoV-2 and, inter alia, pathological changes in the retina. Based on the published findings, we suggest that NRP-1 is a very important mediator implicated in, inter alia, neurological manifestations of SARS-CoV-2 infection. Additionally, it appears that the use of NRP-1 inhibitors is a promising therapeutic strategy for the treatment of SARS-CoV-2 infection.

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Section: Resultsmentioning

confidence: 99%

The Role of Neuropilin-1 (NRP-1) in SARS-CoV-2 Infection: Review

Gudowska-Sawczuk

Mroczko

2021

JCM

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“…Lungs were harvested from mice and single-cell suspensions were prepared as previously described ( Zhao et al, 2020 ). Briefly, the lungs were thoroughly perfused with cold PBS via the left atrium to remove residual blood in the vasculature.…”

Section: Methodsmentioning

confidence: 99%

Injury-induced pulmonary tuft cells are heterogenous, arise independent of key Type 2 cytokines, and are dispensable for dysplastic repair

Barr

Gentile

Lee

et al. 2022

eLife

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While the lung bears significant regenerative capacity, severe viral pneumonia can chronically impair lung function by triggering dysplastic remodeling. The connection between these enduring changes and chronic disease remains poorly understood. We recently described the emergence of tuft cells within Krt5+ dysplastic regions after influenza injury. Using bulk and single cell transcriptomics, we characterized and delineated multiple distinct tuft cell populations that arise following influenza clearance. Distinct from intestinal tuft cells which rely on Type 2 immune signals for their expansion, neither IL-25 nor IL-4ra signaling are required to drive tuft cell development in dysplastic/injured lungs. In addition, tuft cell expansion occurred independently of type I or type III interferon signalling. Furthermore, tuft cells were also observed upon bleomycin injury, suggesting that their development may be a general response to severe lung injury. While intestinal tuft cells promote growth and differentiation of surrounding epithelial cells, in the lungs of tuft cell deficient mice, Krt5+ dysplasia still occurs, goblet cell production is unchanged, and there remains no appreciable contribution of Krt5+ cells into more regionally appropriate alveolar Type 2 cells. Together, these findings highlight unexpected differences in signals necessary for murine lung tuft cell amplification and establish a framework for future elucidation of tuft cell functions in pulmonary health and disease.

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“…In addition to immune markers, RNA-seq data also implicated a significant downregulation (L2FC of À2) in Ki67 (Table S3). Because Ki67 is a prominent proliferation marker that can be used to denote repair (Major et al, 2020;Zhao et al, 2020), we performed immunohistochemistry to ascertain whether our RNA-seq data could be validated independently. To this end, mock and infected lungs from our aged hamster cohorts were fixed and analyzed by H&E staining and probed for Ki67 expression (Figure 1F).…”

Section: Older Hamsters Demonstrate Diminished Innate and Repair Resp...mentioning

confidence: 99%