SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling.

ABSTRACT: Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction within the lung as well as in distal organs. While it is appreciated that an exaggerated inflammatory response is associated with barrier dysfunction, the triggers of this pathology are unclear. Here, we report that cell-intrinsic interactions between the Spike (S) glycoprotein of SARS-CoV-2 and epithelial/endothelial cells are sufficient to trigger barrier dysfunction in vitro and vascular leak in vivo , independently of viral replication and the ACE2 receptor. We identify an S-triggered transcriptional response associated with extracellular matrix reorganization and TGF-β signaling. Using genetic knockouts and specific inhibitors, we demonstrate that glycosaminoglycans, integrins, and the TGF-

SUBMITTER: Biering SB 

PROVIDER: S-EPMC8687463 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature