SARS-CoV-2 infection reduces Krüppel-Like Factor 2 in human lung autopsy
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Abstract
Acute respiratory distress syndrome (ARDS) occurred in ~12% of hospitalized COVID-19 patients in a recent New York City cohort. Pulmonary endothelial dysfunction, characterized by increased expression of inflammatory genes and increased monolayer permeability, is a major component of ARDS. Vascular leak results in parenchymal accumulation of leukocytes, protein, and extravascular water, leading to pulmonary edema, ischemia, and activation of coagulation associated with COVID-19. Endothelial inflammation further contributes to uncontrolled cytokine storm in ARDS. We have recently demonstrated that Krüppel-like factor 2 (KLF2), a transcription factor which promotes endothelial quiescence and monolayer integrity, is significantly reduced in experimental models of ARDS. Lung inflammation and high-tidal volume ventilation result in reduced KLF2, leading to pulmonary endothelial dysfunction and acute lung injury. Mechanistically, we found that KLF2 is a potent transcriptional activator of Rap guanine nucleotide exchange factor 3 (RAPGEF3) which orchestrates and maintains vascular integrity. Moreover, KLF2 regulates multiple genome-wide association study (GWAS)-implicated ARDS genes. Whether lung KLF2 is regulated by SARS-CoV-2 infection is unknown. Here we report that endothelial KLF2 is significantly reduced in human lung autopsies from COVID-19 patients, which supports that ARDS due to SARS-CoV-2 is a vascular phenotype possibly attributed to KLF2 down-regulation. We provide additional data demonstrating that KLF2 is down-regulated in SARS-CoV infection in mice.
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SciScore for 10.1101/2021.01.15.426691: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization Lung tissue from COVID-19 donors were randomly selected and compared to control lungs which were obtained from organ donors whose lungs were non-transplantable, and without SARS-CoV-2 infection, collected prior to the pandemic. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Immunofluorescence was performed with overnight incubation with primary antibodies to KLF2 and vascular endothelial cadherin (VE-Cad), the latter to delineate endothelial cells. KLF2suggested: NoneSamples were incubated with secondary antibodies anti-goat Alexa 488 and anti-mouse … SciScore for 10.1101/2021.01.15.426691: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization Lung tissue from COVID-19 donors were randomly selected and compared to control lungs which were obtained from organ donors whose lungs were non-transplantable, and without SARS-CoV-2 infection, collected prior to the pandemic. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Immunofluorescence was performed with overnight incubation with primary antibodies to KLF2 and vascular endothelial cadherin (VE-Cad), the latter to delineate endothelial cells. KLF2suggested: NoneSamples were incubated with secondary antibodies anti-goat Alexa 488 and anti-mouse Alexa 647 for 1 hour at room temperature. anti-goatsuggested: Noneanti-mousesuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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