Biochemical and Biophysical Research Communications, Vol.372, No.3, 440-446, 2008
Regulation of brain endothelial cells migration and angiogenesis by P-glycoprotein/caveolin-1 interaction
We have investigated the involvement of P-glycoprotein (P-gp)/caveolin-1 interaction in the regulation of brain endothelial cells (EC) migration and tubulogenesis. P-gp overexpression in MDCK-MDR cells was correlated with enhanced cell migration whereas treatment with P-gp inhibitors CsA OF PSC833 reduced it. Transfection of RBE4 rat brain endothelial cells with mutated versions of MDR1, in the caveolin-1 interaction motif, decreased the interaction between P-gp and caveolin-1, enhanced P-gp transport activity and cell migration. Moreover, down-regulation of caveolin-1 in RBE4 cells by siRNA against caveolin-1 stimulated cell migration. Interestingly, the inhibition of P-gp/caveolin-1 interaction increased also EC tubulogenesis. Furthermore, decrease of P-gp expression by siRNA inhibited EC tubulogenesis. These data indicate that the level of P-gp/caveolin-1 interaction can modulate brain endothelial angiogenesis and P gp dependent cell migration. (C) 2008 Elsevier Inc. All rights reserved.
Keywords:P-glycoprotein;caveolin-1;endothelial cells;migration;blood-brain barrier;tubulogenesis;caveolae