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PI3KC2β inactivation stabilizes VE-cadherin junctions and preserves vascular integrity

Anquetil, T; Solinhac, R; Jaffre, A; Chicanne, G; Viaud, J; Darcourt, J; Orset, C; ... Gratacap, M-P; + view all (2021) PI3KC2β inactivation stabilizes VE-cadherin junctions and preserves vascular integrity. EMBO Reports , 22 (6) , Article e51299. 10.15252/embr.202051299. Green open access

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Abstract

Endothelium protection is critical, because of the impact of vascular leakage and edema on pathological conditions such as brain ischemia. Whereas deficiency of class II phosphoinositide 3‐kinase alpha (PI3KC2α) results in an increase in vascular permeability, we uncover a crucial role of the beta isoform (PI3KC2β) in the loss of endothelial barrier integrity following injury. Here, we studied the role of PI3KC2β in endothelial permeability and endosomal trafficking in vitro and in vivo in ischemic stroke. Mice with inactive PI3KC2β showed protection against vascular permeability, edema, cerebral infarction, and deleterious inflammatory response. Loss of PI3KC2β in human cerebral microvascular endothelial cells stabilized homotypic cell–cell junctions by increasing Rab11‐dependent VE‐cadherin recycling. These results identify PI3KC2β as a potential new therapeutic target to prevent aggravating lesions following ischemic stroke.

Type: Article
Title: PI3KC2β inactivation stabilizes VE-cadherin junctions and preserves vascular integrity
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/embr.202051299
Publisher version: https://doi.org/10.15252/embr.202051299
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Endosomal trafficking; endothelial hyperpermeability; phospho-inositide 3-kinase C2b; vascular biology; vascular endothelial-cadherin
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10127156
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