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PI3KC2β inactivation stabilizes VE‐cadherin junctions and preserves vascular integrity
Author(s) -
Anquetil Typhaine,
Solinhac Romain,
Jaffre Aude,
Chicanne Gaëtan,
Viaud Julien,
Darcourt Jean,
Orset Cyrille,
Geuss Eva,
Kleinschnitz Christoph,
Vanhaesebroeck Bart,
Vivien Denis,
Hnia Karim,
Larrue Vincent,
Payrastre Bernard,
Gratacap MariePierre
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202051299
Subject(s) - cadherin , ve cadherin , microbiology and biotechnology , biology , chemistry , biochemistry , cell
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.