@article{621,
  author = {Rina Hashimoto and Junya Takahashi and Keisuke Shirakura and Risa Funatsu and Kaori Kosugi and Sayaka Deguchi and Masaki Yamamoto and Yugo Tsunoda and Maaya Morita and Kosuke Muraoka and Masato Tanaka and Tomoaki Kanbara and Shota Tanaka and Shigeyuki Tamiya and Nagisa Tokunoh and Atsushi Kawai and Masahito Ikawa and Chikako Ono and Keisuke Tachibana and Masuo Kondoh and Masanori Obana and Yoshiharu Matsuura and Akihiro Ohsumi and Takeshi Noda and Takuya Yamamoto and Yasuo Yoshioka and Yu-suke Torisawa and Hiroshi Date and Yasushi Fujio and Miki Nagao and Kazuo Takayama and Yoshiaki Okada},
  title = {SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression},
  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.
          , 
            Organ-on-a-chip technology elucidates the mechanism of SARS-CoV-2 infection–mediated disruption of respiratory vascular barrier.},
  year = {2022},
  journal = {Science Advances},
  volume = {8},
  pages = {eabo6783},
  month = {2022-09-23},
  issn = {2375-2548},
  url = {https://www.science.org/doi/10.1126/sciadv.abo6783},
  doi = {10.1126/sciadv.abo6783},
  language = {en},
}