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| Status |
Public on Sep 22, 2022 |
| Title |
SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
In the initial process of COVID-19, SARS-CoV-2 infects respiratory epithelial cells and then transfers to other organs via 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 (VE-cadherin)-mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in a COVID-19 patient’s lungs were decreased. CLDN5 overexpression or Fluvastatin treatment could rescue the SARS-CoV-2-induced respiratory endothelial barrier disruption. We therefore concluded that the downregulation 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 novel therapeutic strategy against COVID-19.
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| Overall design |
The PET membrane to which HMVEC-L was adhered was mechanically recovered from the airway-on-a-chip, and then total RNA was collected and RNA-seq was performed.
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| |
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| Contributor(s) |
Takayama K |
| Citation(s) |
36129989 |
| |
| Submission date |
Feb 04, 2022 |
| Last update date |
Oct 26, 2022 |
| Contact name |
Kazuo Takayama |
| E-mail(s) |
[email protected]
|
| Phone |
+81-75-366-7362
|
| Organization name |
Kyoto University
|
| Department |
Center for iPS Cell Research and Application
|
| Street address |
Shogoin Kawaharacho 53, Sakyo-ku
|
| City |
Kyoto |
| State/province |
Kyoto |
| ZIP/Postal code |
6068507 |
| Country |
Japan |
| |
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| Platforms (1) |
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| Samples (6)
|
| GSM5860223 |
HMVEC-L of uninfected airway-on-a-chips rep1 |
| GSM5860224 |
HMVEC-L of uninfected airway-on-a-chips rep2 |
| GSM5860225 |
HMVEC-L of uninfected airway-on-a-chips rep3 |
| GSM5860226 |
HMVEC-L of SARS-CoV-2 infected airway-on-a-chips rep1 |
| GSM5860227 |
HMVEC-L of SARS-CoV-2 infected airway-on-a-chips rep2 |
| GSM5860228 |
HMVEC-L of SARS-CoV-2 infected airway-on-a-chips rep3 |
|
| Relations |
| BioProject |
PRJNA803375 |
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