Mechanism of hyperpermeability induced by vascular endothelial growth factor in glomerular endothelial cells through Racl activation
10.3760/cma.j.issn.1001-7097.2009.02.009
- VernacularTitle:血管内皮细胞生长因子激活Rac 1引起肾小球内皮细胞通透性增高的机制
- Author:
Hui PENG
;
Jun ZHANG
;
Cheng WANG
;
Zhujiang CHEN
;
Chenggang SHI
;
Tanqi LOU
- Publication Type:Journal Article
- Keywords:
Endothelial growth factors;
Racl GTP-binding protein;
Tight junctions;
Endothelial cells;
Permeability
- From:
Chinese Journal of Nephrology
2009;25(2):111-115
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate if Rac1 GTPase activation plays an important role in hyperpermeability and tyresine phosphorylation of tight junction induced by vascular endothelial growth factor (VEGF) in glomertdar endothelial cells (GEnCs). Methods Primary cultured rat endothelial cells were used as experimental model. The effect of VEGF at different concentrations (5 or 50 μg/L) on endothelial permeability was investigated by transendothelial electrical resistance (TEER). The permeability of GEnCs transfected with wild type Rac1 (wtRacl) or dominant negative Racl (N17Rac1) was also detected. Immune precipitation and immune blotting were used to detect the tyrosine phosphor-occludin in GEnCs. Results VEGF at high concentration (50 μg/L) induced hyperpermeability in GEnCs (P<0.05). At the same time, GTP-binding and membrane-bound Racl GTPase significantly increased(P<0.01)in GEnCs. Tyrosine phosphor-occludin was also increased (P<0.05) under VEGF stimulation. However, transfection of GEnCs with N17Rac1 dramatically attenuated the effect of VEGF on tyrosine phospho-occludin and endothelial cell permeability. Conclusions Increased VEGF can induce hyperpermeability in glomerular endothelial cells, which is related to occludin tyrosine phosphorylation through Racl activation. It provides a framework for understanding the role of VEGF-induced Racl-phospho-occludin pathway in the integrity of barrier function in the diabetic milieu.
