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. 2008 Aug 1;372(3):440-6.
doi: 10.1016/j.bbrc.2008.05.012. Epub 2008 May 15.

Regulation of brain endothelial cells migration and angiogenesis by P-glycoprotein/caveolin-1 interaction

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Regulation of brain endothelial cells migration and angiogenesis by P-glycoprotein/caveolin-1 interaction

Stéphane Barakat et al. Biochem Biophys Res Commun. .

Abstract

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 or 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.

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