Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection - 06/09/22
, Zheng Zhang a, d, e, ⁎
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Highlights |
• | The expression of ACE2 in infected cells was down-regulated during SARS-CoV-2 infection. |
• | SARS-CoV-2 S protein activates intracellular signaling to destabilize ACE2 mRNA. |
• | In patients with COVID-19, ACE2 decreased in the pulmonary bronchial region, Ang II level increased in plasma, and pulmonary vascular damage was obvious. |
• | The downregulation of ACE2 mediated by Spike protein potentially links COVID-19 to the imbalance of RAS. |
Summary |
The ongoing global pandemic of Coronavirus disease 2019 (COVID-19) poses a serious threat to human health, with patients reportedly suffering from thrombus, vascular injury and coagulation in addition to acute and diffuse lung injury and respiratory diseases. Angiotensin converting enzyme 2 (ACE2) as the receptor for SARS-CoV-2 entry, is also an important regulator of renin-angiotensin system (RAS) homeostasis, which plays an unsettled role in the pathogenesis of COVID-19. Here, we demonstrated that SARS-CoV-2 Spike protein activated intracellular signals to degrade ACE2 mRNA. The decrease of ACE2 and higher level of angiotensin (Ang) II were verified in COVID-19 patients. High dose of Ang II induced pulmonary artery endothelial cell death in vitro, which was also observed in the lung of COVID-19 patients. Our finding indicates that the downregulation of ACE2 potentially links COVID-19 to the imbalance of RAS.
Le texte complet de cet article est disponible en PDF.Key words : SARS-CoV-2, Spike, ACE2, Ang II
Abbreviations : COVID-19, SARS-CoV-2, RAS, Ang I, Ang II, AT1R, AT2R, HPAEC, c-casp3, VWF, TCID50, WB, IHC, PVDF, BSA, rhACE2, SPP, DAB, ACE, ACE2
Plan
Vol 85 - N° 4
P. 418-427 - octobre 2022 Retour au numéro
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