Cannabidiol Increases Proliferation, Migration, Tubulogenesis, and Integrity of Human Brain Endothelial Cells through TRPV2 Activation. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Molecular Pharmaceutics Année : 2019

Cannabidiol Increases Proliferation, Migration, Tubulogenesis, and Integrity of Human Brain Endothelial Cells through TRPV2 Activation.

N Perrière
  • Fonction : Auteur
Dm Smadja
  • Fonction : Auteur
Mc Menet
  • Fonction : Auteur
Po Couraud
  • Fonction : Auteur
X. Declèves
  • Fonction : Auteur
Huilong Luo
  • Fonction : Auteur
Elisa Rossi
Bruno Saubamea
Steṕhanie Chasseigneaux
  • Fonction : Auteur
Veŕonique Cochois
  • Fonction : Auteur
Nina Choublier
  • Fonction : Auteur
Maria Smirnova
  • Fonction : Auteur
Fabienne Glacial
  • Fonction : Auteur
Nicolas Perriere
  • Fonction : Auteur
Sandrine Bourdoulous
David Smadja
Marie-Claude Menet
  • Fonction : Auteur
Pierre-Olivier Couraud
  • Fonction : Auteur
Salvatore Cisternino
Xavier Decleves

Résumé

The effect of cannabidiol (CBD), a high-affinity agonist of the transient receptor potential vanilloid-2 (TRPV2) channel, has been poorly investigated in human brain microvessel endothelial cells (BMEC) forming the blood−brain barrier (BBB). TRPV2 expression and its role on Ca 2+ cellular dynamics, trans-endothelial electrical resistance (TEER), cell viability and growth, migration, and tubulogenesis were evaluated in human primary cultures of BMEC (hPBMEC) or in the human cerebral microvessel endothelial hCMEC/D3 cell line. Abundant TRPV2 expression was measured in hCMEC/D3 and hPBMEC by qRT-PCR, Western blotting, nontargeted proteomics, and cellular immunofluorescence studies. Intracellular Ca 2+ levels were increased by heat and CBD and blocked by the nonspecific TRP antagonist ruthenium red (RR) and the selective TRPV2 inhibitor tranilast (TNL) or by silencing cells with TRPV2 siRNA. CBD dose-dependently induced the hCMEC/D3 cell number (EC 50 0.3 ± 0.1 μM), and this effect was fully abolished by TNL or TRPV2 siRNA. A wound healing assay showed that CBD induced cell migration, which was also inhibited by TNL or TRPV2 siRNA. Tubulogenesis of hCMEC/D3 cells in 3D matrigel cultures was significantly increased by 41 and 73% after a 7 or 24 h CBD treatment, respectively, and abolished by TNL. CBD also increased the TEER of hPBMEC monolayers cultured in transwell, and this was blocked by TNL. Our results show that CBD, at extracellular concentrations close to those observed in plasma of patients treated by CBD, induces proliferation, migration, tubulogenesis, and TEER increase in human brain endothelial cells, suggesting CBD might be a potent target for modulating the human BBB.
Fichier non déposé

Dates et versions

hal-02408215 , version 1 (12-12-2019)

Identifiants

Citer

N Perrière, Dm Smadja, Mc Menet, Po Couraud, X. Declèves, et al.. Cannabidiol Increases Proliferation, Migration, Tubulogenesis, and Integrity of Human Brain Endothelial Cells through TRPV2 Activation.. Molecular Pharmaceutics, 2019, ⟨10.1021/acs.molpharmaceut.8b01252⟩. ⟨hal-02408215⟩
57 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More