| Vascular endothelium is composed of monolayer endothelial cells(endothelial cells, ECs). Endothelial cells are arranged closely to provide a smooth cavosurface for the intravascular lumen, provide blood flow with smooth surface, form good blood flow dynamics environment. Vascular endothelium is the main barrier to regulate blood and surrounding tissue of material exchange. It is also a layer of semi-selective permeability barrier of the vascular cavity surface.Vascular endothelial barrier dysfunction is one of the main characteristics of the diseases such as inflammation and atherosclerosis.The precise regulation of vascular endothelial cell permeability is the basis of sustaining cyclic steady state and normal physiological functions of various organs. The increase of permeability is usually as an important indicator of testing endothelial barrier function. Various stimulus cause endothelial cell permeability increase, lots of inflammatory and thrombosis medium can damage endothelial barrier function, lead to higher permeability, plasma protein extravasation and cause oedema of tissues〠organs and dysfunction. Which inflammation early release of tumor necrosis factor a (TNF-α) is an important cell factor of causing vascular endothelial permeability increasing and play an important role for the development of inflammation. Maintain normal barrier function depends on the dynamic balance between centrifugal force caused by cytoskeleton contraction and the adhesion force between cells connected.Glutathione S-transferases (GSTs) is a kind of super family isozyme of xenobiotic metabolism in vivo, including Alpha, Mu, PI and other seven subtypes. GSTpi (GSTpi) is one of the most abundant subtypes in mammals, not only can participate in the removal of the intracellular ROS, but also can through the combination between protein and influence the activity of a series of signal molecules in cells. Studies have found that GSTpi as anti-inflammatory factors involved in regulating inflammation caused by the LPS and TNF-a and GSTpi played an important role in intracellular MAPKs pathway. However, GSTpi in inflammation induced vascular endothelial dysfunction has not been reported. The purpose of this study is to investigate whether the GSTpi can by acting on related signaling molecule in cells, inhibition of VE-cadherin endocytosis, inhibit the reshaping of the cytoskeleton, thus inhibiting vascular endothelial permeability increase caused by the inflammatory response.In this experiment, we use Transwell assay to detect the role of GSTpi in endothelial cells permeability increase induced by TNF-a. By confocal laser scanning technology, the fuction of GSTpi remodeling cytoskeleton and membrane surface VE-cadherin redistribution of TNF-a-induced endothelial cells are detected. And western blotting is used to detect the effect of over-expressed GSTpi on the membrane surface VE-cadherin redistribution and p38 phosphorylation level.GSTpi suppressed TNF-a-induced endothelial permeability increase by influencing the ECs skeleton remodeling and membrane surface VE-cadherin endocytosis. Inhibition of GSTpi enzyme activity enhanced the increases of endothelial permeability induced by TNF-a. Inhibiting intracellular p38 phosphorylation level significantly, GSTpi inhibited membrane surface VE-cadherin endocytosis and the increase of endothelial permeability.This study confirmed that GSTpi played an important role in the TNF-a-induced endothelial cells permeability increase, which was associated with the involvement of GSTpi in the inhibition of p38 phosphorylation. GSTpi regulated the remodeling of Actin cytoskeleton and VE-cadherin endocytosis induced by TNF-a through regulating p38 phosphorylation level, thus inhibited the increase of TNF-a-induced endothelial cells permeability. In conclusion, GSTpi played an important role in resisting vascular endothelial barrier dysfunction caused by inflammation. |
