{"doi":"10.1101/2021.01.15.426691","title":"SARS-CoV-2 infection reduces Krüppel-Like Factor 2 in human lung autopsy","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 Kruppel-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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":216330,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.96,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":680555,"name":"David Wu","orcid":"0000-0003-3162-3238","position":1,"is_corresponding":false},{"id":722955,"name":"Robert D. Guzy","orcid":"0000-0001-8420-6177","position":2,"is_corresponding":false},{"id":572763,"name":"Nathan Schoettler","orcid":"0000-0001-9851-6352","position":3,"is_corresponding":false},{"id":285949,"name":"Ayodeji Adegunsoye","orcid":"0000-0002-7015-9610","position":4,"is_corresponding":false},{"id":535133,"name":"Jeffrey Mueller","orcid":"0009-0009-5839-0578","position":5,"is_corresponding":false},{"id":812754,"name":"Aliya Hussein","orcid":null,"position":6,"is_corresponding":false},{"id":285956,"name":"Anne I. Sperling","orcid":"0000-0002-4265-9212","position":7,"is_corresponding":false},{"id":625428,"name":"Gökhan M. Mutlu","orcid":"0000-0002-2056-612X","position":8,"is_corresponding":false},{"id":348231,"name":"Yun Fang","orcid":"0000-0003-4597-3095","position":9,"is_corresponding":false},{"id":812238,"name":"Tzu-Han Lee","orcid":"0000-0002-8488-2113","position":0,"is_corresponding":true}],"reference_count":12,"raw_metadata":null,"created_at":"2026-07-18T23:53:11.245932Z","pmid":"33469586","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}