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10.1101/2021.12.10.472112 http://scihub22266oqcxt.onion/10.1101/2021.12.10.472112 34931188!8687463!34931188     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       bioRxiv 2021 ; ä (ä): ä Nephropedia Template TP {{tp|p=34931188|t=2021. SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-beta signaling |pdf=|usr=}}{{34931188}} gab.com Text SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-beta signaling JO: bioRxiv http://www.kidney.de/pget.php?&tw=1&pmid=34931188 #FOAvip 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-beta signaling. Using genetic knockouts and specific inhibitors, we demonstrate that glycosaminoglycans, integrins, and the TGF-beta signaling axis are required for S-mediated barrier dysfunction. Our findings suggest that S interactions with barrier cells are a contributing factor to COVID-19 disease severity and offer mechanistic insight into SARS-CoV-2 triggered vascular leak, providing a starting point for development of therapies targeting COVID-19 pathogenesis. Twit Text FOAVip SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-beta signaling ????bioRxiv http://www.kidney.de/pget.php?&tw=1&pmid=34931188 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34931188 #FOAvip English Wikipedia <ref>{{Cite pmid|34931188}}</ref> SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-beta signaling #MMPMID34931188 Biering SB; de Sousa FTG; Tjang LV; Pahmeier F; Ruan R; Blanc SF; Patel TS; Worthington CM; Glasner DR; Castillo-Rojas B; Servellita V; Lo NTN; Wong MP; Warnes CM; Sandoval DR; Clausen TM; Santos YA; Ortega V; Aguilar HC; Esko JD; Chui CY; Pak JE; Beatty PR; Harris E bioRxiv 2021[Dec]; ä (ä): ä PMID34931188show ga 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-beta signaling. Using genetic knockouts and specific inhibitors, we demonstrate that glycosaminoglycans, integrins, and the TGF-beta signaling axis are required for S-mediated barrier dysfunction. Our findings suggest that S interactions with barrier cells are a contributing factor to COVID-19 disease severity and offer mechanistic insight into SARS-CoV-2 triggered vascular leak, providing a starting point for development of therapies targeting COVID-19 pathogenesis. äSARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via in(epmc).pdf DeepDyve Pubget Overpricing