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タイトル: | SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression |
著者: | 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 https://orcid.org/0000-0002-0658-4663 (unconfirmed) Yamamoto, Takuya https://orcid.org/0000-0002-0022-3947 (unconfirmed) Yoshioka, Yasuo Torisawa, Yu-suke Date, Hiroshi Fujio, Yasushi Nagao, Miki https://orcid.org/0000-0002-8886-6145 (unconfirmed) Takayama, Kazuo https://orcid.org/0000-0002-1132-2457 (unconfirmed) Okada, Yoshiaki |
著者名の別形: | 橋本, 里菜 高橋, 潤也 白倉, 圭佑 船津, 梨彩 小杉, 佳織 出口, 清香 山本, 正樹 角田, 優伍 森田, 真綾 村岡, 康介 田中, 雅人 神原, 知明 田中, 翔大 民谷, 繁幸 徳納, 渚沙 河合, 惇志 伊川, 正人 小野, 慎子 橘, 敬祐 近藤, 昌夫 尾花, 理徳 松浦, 善治 大角, 明宏 野田, 岳志 山本, 拓也 吉岡, 靖雄 鳥澤, 勇介 伊達, 洋至 藤尾, 慈 長尾, 美紀 高山, 和雄 岡田, 欣晃 |
発行日: | Sep-2022 |
出版者: | American Association for the Advancement of Science (AAAS) |
誌名: | Science Advances |
巻: | 8 |
号: | 38 |
論文番号: | eabo6783 |
抄録: | 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. |
記述: | 臓器チップ技術を用いて新型コロナウイルスが血管へ侵入するメカニズムを解明 --Claudin-5発現抑制による呼吸器の血管内皮バリア破壊--. 京都大学プレスリリース. 2022-09-22. A study using an organ-on-a-chip reveals a mechanism of SARS-CoV-2 invasion into blood vessels --Disruption of vascular endothelial barrier in respiratory organs by decreasing Claudin-5 expression--. 京都大学プレスリリース. 2022-09-27. |
著作権等: | Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
URI: | http://hdl.handle.net/2433/276366 |
DOI(出版社版): | 10.1126/sciadv.abo6783 |
PubMed ID: | 36129989 |
関連リンク: | https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/220922-030000.html https://www.cira.kyoto-u.ac.jp/e/pressrelease/news/220927-150001.html |
出現コレクション: | 学術雑誌掲載論文等 |
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