Role of endothelial cell injury in the pathogenesis of diabetic nephropathy / 中国糖尿病杂志

[Summary] Diabetic nephropathy is one of the major chronic microvascular complications of diabetes ,which is the leading cause of end‐stage renal disease ,as well as the main cause of death in diabetic patients. Glomerular endothelial cell is an important component of the glomerular filtration barrier ,which is directly related to the materials of circulation ,and it can be easily damaged by glucose ,lipid and inflammatory factors. Under the hyperglycemia ,the PKC pathway ,the polyol pathway and oxidative stress were activated ,producing an excess of advanced glycation end products and reactive oxygen species ,which damage the endothelial nitric oxide synthase ,reduce the generation of nitric oxide ,while produce a large number of Ang Ⅱ. Ang Ⅱ damage the endothelial cell. In addition ,there are crosstalk between glomerular endothelial cells and endothelial cells ,which also cause endothelial cell injury. Here ,we reviewed the role of endothelial cell injury in the pathogenesis of diabetic nephropathy.

Transforming growth factor-beta and the glomerular filtration barrier

The increasing burden of chronic kidney disease worldwide and recent advancements in the understanding of pathologic events leading to kidney injury have opened up new potential avenues for therapies to further diminish progression of kidney disease by targeting the glomerular filtration barrier and reducing proteinuria. The glomerular filtration barrier is affected by many different metabolic and immune-mediated injuries. Glomerular endothelial cells, the glomerular basement membrane, and podocytes-the three components of the filtration barrier-work together to prevent the loss of protein and at the same time allow passage of water and smaller molecules. Damage to any of the components of the filtration barrier can initiate proteinuria and renal fibrosis. Transforming growth factor-beta (TGF-beta) is a pleiotropic cytokine strongly associated with the fibrogenic response.It has a known role in tubulointerstitial fibrosis. In this review we will highlight what is known about TGF-beta and how it interacts with the components of glomerular filtration barrier and causes loss of function and proteinuria.

Transforming growth factor-beta and the glomerular filtration barrier

The increasing burden of chronic kidney disease worldwide and recent advancements in the understanding of pathologic events leading to kidney injury have opened up new potential avenues for therapies to further diminish progression of kidney disease by targeting the glomerular filtration barrier and reducing proteinuria. The glomerular filtration barrier is affected by many different metabolic and immune-mediated injuries. Glomerular endothelial cells, the glomerular basement membrane, and podocytes-the three components of the filtration barrier-work together to prevent the loss of protein and at the same time allow passage of water and smaller molecules. Damage to any of the components of the filtration barrier can initiate proteinuria and renal fibrosis. Transforming growth factor-beta (TGF-beta) is a pleiotropic cytokine strongly associated with the fibrogenic response.It has a known role in tubulointerstitial fibrosis. In this review we will highlight what is known about TGF-beta and how it interacts with the components of glomerular filtration barrier and causes loss of function and proteinuria.

Upregulation of sFlt-1 by Trophoblasts Induces the Barrier Dysfunction of Glomerular Endothelial Cells / 华中科技大学学报（医学）（英德文版）

This study examined the effect of over-expression of sFlt-1 by trophoblasts on the barrier function of glomerular endothelial cells and the role of VEGF in this process in order to explore the pathogenesis of glomerular disease in preeclampsia.SFlt-1 expression in the human trophoblasts (TEV-1 cells) was enhanced by transfecting sFlt-1 plasmid DNA into TEV-1 cells.The monolayer barrier function of glomerular endothelial cells (ciGEnCs) was determined by measuring the fluorescence intensity of bovine serum albumin (BSA) that crossed the monolayer of glomerular endothelial cells.The results showed that the over-expression of sFlt-1 by TEV-1 cells led to the barrier dysfunction of ciGEnCs,and the exogenous VEGF could alleviate the ciGEnCs dysfunction resulting from the over-expression of sFlt-1 to a certain extent.It was concluded that the dysregulation of sFlt-1 and VEGF in preeclamptic pregnancy may contribute to the barrier dysfunction of glomerular endothelial cells,and VEGF may play an important role in maintaining the barrier function of glomerular endothelial cells,but it may not be the sole factor.