SARS-CoV-2 Disrupts Respiratory Vascular Barriers by Suppressing Claudin-5 Expression

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2022 Sep 21

PMID 36129989

Authors

Rina Hashimoto

Junya Takahashi

Keisuke Shirakura

Risa Funatsu

Kaori Kosugi

Sayaka Deguchi

Masaki Yamamoto

Yugo Tsunoda

Maaya Morita

Kosuke Muraoka

Masato Tanaka

Tomoaki Kanbara

Shota Tanaka

Shigeyuki Tamiya

Nagisa Tokunoh

Atsushi Kawai

Masahito Ikawa

Chikako Ono

Keisuke Tachibana

Masuo Kondoh

Masanori Obana

Yoshiharu Matsuura

Akihiro Ohsumi

Takeshi Noda

Takuya Yamamoto

Yasuo Yoshioka

Yu-Suke Torisawa

Hiroshi Date

Yasushi Fujio

Miki Nagao

Kazuo Takayama

Yoshiaki Okada

Affiliations

Soon will be listed here.

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.

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