Induction of blood-brain barrier differentiation in a rat brain-derived endothelial cell line
Résumé
An immortalized brain capillary endothelial cell line displaying blood-brain barrier characteristics may represent a useful tool for studying blood-brain barrier endothelial cell differentiation and for the in vitro prediction of drug brain penetration. In the present study, we have established a rat cerebral capillary endothelial cell line (CR3) by genomic introduction of the immortalizing SV40 large T gene under the control of the human vimentin promoter. The CR3 cell line displayed endothelial morphological and biochemical characteristics for up to 30 passages. However, the CR3 cell line did not spontaneously express the specific blood-brain barrier markers gamma-glutamyl transpeptidase and mdr P-glycoprotein. However, when the cells were treated with the cell differentiating agent all-trans-retinoic acid, the blood-brain barrier markers were induced. Retinoic acid-treated CR3 cells may thus represent a useful tool for biological and pharmacological research related to the blood-brain barrier.
Mots clés
Animals
Biomarkers
Blood-Brain Barrier/*physiology
Brain/cytology/*physiology
Capillaries/cytology/physiology
Cell Differentiation
Cell Line/cytology/*physiology
Cell Transformation
Viral
Culture Techniques/methods
Endothelium
Vascular/cytology/*physiology
Fluorescent Antibody Technique
Karyotyping
Lipoproteins
LDL/metabolism
P-Glycoprotein/analysis
Rats
Vimentin/isolation & purification
Vinblastine/metabolism
gamma-Glutamyltransferase/analysis
von Willebrand Factor/isolation & purification