Abstract
In the initial process of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects respiratory epithelial cells and then transfers to other organs the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin-mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in the lungs of a patient with COVID-19 were decreased. CLDN5 overexpression or Fluvastatin treatment rescued the SARS-CoV-2-induced respiratory endothelial barrier disruption. We concluded that the down-regulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2-induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a therapeutic strategy against COVID-19.
【초록키워드】 COVID-19, Treatment, coronavirus disease, SARS-CoV-2, coronavirus, lung, Protein, blood vessels, expression, mechanism, therapeutic strategy, epithelial cell, endothelial, acute respiratory syndrome, Vascular, junctions, transfer, down-regulation, protein expression, overexpression, organ, infect, patient with COVID-19, fluvastatin, initial, produced, investigated, disrupt, disrupting, rescued, respiratory epithelial cell, CLDN5, other organ, 【제목키워드】 SARS-CoV-2, expression, Vascular, disrupt,