TY - JOUR
AU - Rina Hashimoto
AU - Junya Takahashi
AU - Keisuke Shirakura
AU - Risa Funatsu
AU - Kaori Kosugi
AU - Sayaka Deguchi
AU - Masaki Yamamoto
AU - Yugo Tsunoda
AU - Maaya Morita
AU - Kosuke Muraoka
AU - Masato Tanaka
AU - Tomoaki Kanbara
AU - Shota Tanaka
AU - Shigeyuki Tamiya
AU - Nagisa Tokunoh
AU - Atsushi Kawai
AU - Masahito Ikawa
AU - Chikako Ono
AU - Keisuke Tachibana
AU - Masuo Kondoh
AU - Masanori Obana
AU - Yoshiharu Matsuura
AU - Akihiro Ohsumi
AU - Takeshi Noda
AU - Takuya Yamamoto
AU - Yasuo Yoshioka
AU - Yu-suke Torisawa
AU - Hiroshi Date
AU - Yasushi Fujio
AU - Miki Nagao
AU - Kazuo Takayama
AU - Yoshiaki Okada
AB - 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.
BT - Science Advances
DA - 2022-09-23
DO - 10.1126/sciadv.abo6783
IS - 38
LA - en
N2 - 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.
PY - 2022
EP - eabo6783
T2 - Science Advances
TI - SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression
UR - https://www.science.org/doi/10.1126/sciadv.abo6783
VL - 8
Y2 - 2022-10-04
SN - 2375-2548
ER -