PI3KC2β inactivation stabilizes VE-cadherin junctions and preserves vascular integrity.
endosomal trafficking
endothelial hyperpermeability
phosphoinositide 3-kinase C2β
vascular biology
vascular endothelial-cadherin
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
04 06 2021
04 06 2021
Historique:
revised:
02
03
2021
received:
10
07
2020
accepted:
12
03
2021
pubmed:
22
4
2021
medline:
29
6
2021
entrez:
21
4
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33880878
doi: 10.15252/embr.202051299
pmc: PMC8183416
doi:
Substances chimiques
Antigens, CD
0
Cadherins
0
cadherin 5
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e51299Subventions
Organisme : Nouvelle Société Française d'Athérosclérose
Organisme : Fondation de France
ID : 00056850
Organisme : Agence Nationale de la Recherche (ANR)
ID : ANR-16-CE14-0009-01
Organisme : Fondation pour la Recherche Médicale (FRM)
ID : DEQ20170336737
Informations de copyright
© 2021 The Authors.
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