Regulation of brain endothelial cells migration and angiogenesis by P-glycoprotein/caveolin-1 interaction
- 作者：Sté ; phane Barakat ; S ; ra Turcotte ; Michel Demeule ; Marie-Paule Lachambre ; Anthony Ré ; gina ; Loris G. Baggetto ; Richard Bé ; liveau
- 关键词：P-glycoprotein ; Caveolin-1 ; Endothelial cells ; Migration ; Blood– ; brain barrier ; Tubulogenesis ; Caveolae
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2008
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：1 August 2008
- 卷：372
- 期：3
- 页码：440-446
- 文件大小：605 K
摘要
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.