tetano
Editor, Senior Moderator
Sci Adv
. 2022 Sep 23;8(38):eabo6783.
doi: 10.1126/sciadv.abo6783. Epub 2022 Sep 21.
SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression
Rina Hashimoto[SUP] 1 [/SUP], Junya Takahashi[SUP] 2 [/SUP], Keisuke Shirakura[SUP] 2 [/SUP], Risa Funatsu[SUP] 2 [/SUP], Kaori Kosugi[SUP] 1 [/SUP], Sayaka Deguchi[SUP] 1 [/SUP], Masaki Yamamoto[SUP] 3 [/SUP], Yugo Tsunoda[SUP] 4 5 [/SUP], Maaya Morita[SUP] 2 [/SUP], Kosuke Muraoka[SUP] 2 [/SUP], Masato Tanaka[SUP] 2 [/SUP], Tomoaki Kanbara[SUP] 2 [/SUP], Shota Tanaka[SUP] 2 [/SUP], Shigeyuki Tamiya[SUP] 6 [/SUP], Nagisa Tokunoh[SUP] 6 7 [/SUP], Atsushi Kawai[SUP] 2 6 [/SUP], Masahito Ikawa[SUP] 2 6 8 [/SUP], Chikako Ono[SUP] 6 8 [/SUP], Keisuke Tachibana[SUP] 2 [/SUP], Masuo Kondoh[SUP] 2 [/SUP], Masanori Obana[SUP] 2 9 10 [/SUP], Yoshiharu Matsuura[SUP] 6 8 [/SUP], Akihiro Ohsumi[SUP] 11 [/SUP], Takeshi Noda[SUP] 4 5 [/SUP], Takuya Yamamoto[SUP] 1 12 13 [/SUP], Yasuo Yoshioka[SUP] 2 6 7 8 9 10 [/SUP], Yu-Suke Torisawa[SUP] 14 [/SUP], Hiroshi Date[SUP] 11 [/SUP], Yasushi Fujio[SUP] 2 8 9 [/SUP], Miki Nagao[SUP] 3 [/SUP], Kazuo Takayama[SUP] 1 15 [/SUP], Yoshiaki Okada[SUP] 2 8 [/SUP]
Affiliations
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
. 2022 Sep 23;8(38):eabo6783.
doi: 10.1126/sciadv.abo6783. Epub 2022 Sep 21.
SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression
Rina Hashimoto[SUP] 1 [/SUP], Junya Takahashi[SUP] 2 [/SUP], Keisuke Shirakura[SUP] 2 [/SUP], Risa Funatsu[SUP] 2 [/SUP], Kaori Kosugi[SUP] 1 [/SUP], Sayaka Deguchi[SUP] 1 [/SUP], Masaki Yamamoto[SUP] 3 [/SUP], Yugo Tsunoda[SUP] 4 5 [/SUP], Maaya Morita[SUP] 2 [/SUP], Kosuke Muraoka[SUP] 2 [/SUP], Masato Tanaka[SUP] 2 [/SUP], Tomoaki Kanbara[SUP] 2 [/SUP], Shota Tanaka[SUP] 2 [/SUP], Shigeyuki Tamiya[SUP] 6 [/SUP], Nagisa Tokunoh[SUP] 6 7 [/SUP], Atsushi Kawai[SUP] 2 6 [/SUP], Masahito Ikawa[SUP] 2 6 8 [/SUP], Chikako Ono[SUP] 6 8 [/SUP], Keisuke Tachibana[SUP] 2 [/SUP], Masuo Kondoh[SUP] 2 [/SUP], Masanori Obana[SUP] 2 9 10 [/SUP], Yoshiharu Matsuura[SUP] 6 8 [/SUP], Akihiro Ohsumi[SUP] 11 [/SUP], Takeshi Noda[SUP] 4 5 [/SUP], Takuya Yamamoto[SUP] 1 12 13 [/SUP], Yasuo Yoshioka[SUP] 2 6 7 8 9 10 [/SUP], Yu-Suke Torisawa[SUP] 14 [/SUP], Hiroshi Date[SUP] 11 [/SUP], Yasushi Fujio[SUP] 2 8 9 [/SUP], Miki Nagao[SUP] 3 [/SUP], Kazuo Takayama[SUP] 1 15 [/SUP], Yoshiaki Okada[SUP] 2 8 [/SUP]
Affiliations
- PMID: 36129989
- DOI: 10.1126/sciadv.abo6783
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