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SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression

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...

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Detalles Bibliográficos
Autores principales: Hashimoto, Rina, Takahashi, Junya, Shirakura, Keisuke, Funatsu, Risa, Kosugi, Kaori, Deguchi, Sayaka, Yamamoto, Masaki, Tsunoda, Yugo, Morita, Maaya, Muraoka, Kosuke, Tanaka, Masato, Kanbara, Tomoaki, Tanaka, Shota, Tamiya, Shigeyuki, Tokunoh, Nagisa, Kawai, Atsushi, Ikawa, Masahito, Ono, Chikako, Tachibana, Keisuke, Kondoh, Masuo, Obana, Masanori, Matsuura, Yoshiharu, Ohsumi, Akihiro, Noda, Takeshi, Yamamoto, Takuya, Yoshioka, Yasuo, Torisawa, Yu-suke, Date, Hiroshi, Fujio, Yasushi, Nagao, Miki, Takayama, Kazuo, Okada, Yoshiaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491726/
https://www.ncbi.nlm.nih.gov/pubmed/36129989
http://dx.doi.org/10.1126/sciadv.abo6783
Descripción
Sumario: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.