Cannabidiol Increases Proliferation, Migration, Tubulogenesis, and Integrity of Human Brain Endothelial Cells through TRPV2 Activation
| Autor: | Nicolas Perrière, Bruno Saubaméa, Sandrine Bourdoulous, David M. Smadja, Stéphanie Chasseigneaux, Huilong Luo, Véronique Cochois, Nina Choublier, Elisa Rossi, Pierre-Olivier Couraud, Maria Smirnova, Xavier Declèves, Salvatore Cisternino, Fabienne Glacial, Marie-Claude Menet |
|---|---|
| Přispěvatelé: | INSEAN - CNR, Consiglio Nazionale delle Ricerche [Roma] (CNR), Laboratoire Kastler Brossel (LKB (Lhomond)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2019 |
| Předmět: |
Hot Temperature
Cell Survival [SDV]Life Sciences [q-bio] TRPV2 TRPV Cation Channels brain endothelial cells Pharmaceutical Science [SDV.BC]Life Sciences [q-bio]/Cellular Biology [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Cell Line cannabidiol 03 medical and health sciences 0302 clinical medicine Cell Movement Drug Discovery Electric Impedance Extracellular Humans ortho-Aminobenzoates Viability assay Microvessel Cannabis Cell Proliferation 030304 developmental biology 0303 health sciences Matrigel Brain Neoplasms Plant Extracts Chemistry Endothelial Cells Cell migration tranilast Ruthenium Red digestive system diseases Cell biology Blood-Brain Barrier Cell culture Microvessels Molecular Medicine Calcium 030217 neurology & neurosurgery Intracellular |
| Zdroj: | Molecular Pharmaceutics Molecular Pharmaceutics, American Chemical Society, 2019, ⟨10.1021/acs.molpharmaceut.8b01252⟩ |
| ISSN: | 1543-8392 1543-8384 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|