The growth factor angiopoietin-1 (Ang1) has been identified as the primary activating ligand for Tie2, a tyrosine kinase receptor highly expressed in vascular endothelial cells. Genetic studies using targeted mutations in mice have demonstrated that Tie2 activation by Ang1 is crucial for angiogenesis, vascular remodelling, and vascular maturation. However, the angiogenic functions of Ang1 are d...

IQGAP1 is a scaffold protein that interacts with proteins of the cytoskeleton and the intercellular adhesion complex. In podocytes, IQGAP1 is associated with nephrin in the glomerular slit diaphragm (SD) complex, but its role remains ill-defined. In this work, we investigated the interaction of IQGAP1 with the cytoskeleton and SD proteins in podocytes in culture, and its role in podocyte migrat...

The conventional paradigm on the pathogenesis of nephrotic syndrome revolves around the concept of a glomerular disorder which is characterized by massive proteinuria with consequent hypoalbuminemia, generalized edema and hyperlipidemia. However, the changes at structural and molecular levels of the podocytes have recently assumed prominence as a new paradigm on the pathogenesis of pediatric id...

Patients with albuminuria and CKD frequently have vascular dysfunction but the underlying mechanisms remain unclear. Because the endothelial surface layer, a meshwork of surface-bound and loosely adherent glycosaminoglycans and proteoglycans, modulates vascular function, its loss could contribute to both renal and systemic vascular dysfunction in proteinuric CKD. Using Munich-Wistar-Fromter (MW...

The present study aimed to investigate the effects of advanced glycation end‑products (AGEs) on the permeability of glomerular endothelial cells (GEnCs) and determine whether enhanced permeability was due to degradation of tight junction (TJ) complexes by matrix metalloproteinases (MMPs). Cultured monolayers of GEnCs were exposed to AGEs at different doses and treatment durations in the presenc...

In animal models, reduced nephron mass impairs renal arteriolar autoregulation, increasing vulnerability of the remaining nephrons to elevated systemic blood pressure (BP). A feature of the resulting glomerular capillary hypertension is an increase in glomerular permeability. We sought evidence of a similar remnant nephron effect in human chronic kidney disease. In participants from the United ...

ANGIOTENSIN II (ANG II), acting on AT1 receptors, results in a variety of physiological effects, such as vasoconstriction, tubular sodium retention, and increased arterial blood pressure (4, 5). Interestingly, increased ANG II signaling also results in increased urinary protein leakage. The increased protein leakage across the glomerular filtration barrier has classically been attributed to the...

At 30 minutes after intravenous administration of the glomerular renal agent TC-99m-DTPA, both right and left lateral views were obtained. We analyzed the ratio of optical densities (behind the ureter/In front of the ureter). In patients without gross renal failure or retroperitoneal disease, the ratio was always less than 1 (range 0.38 to 0.95, mean 0.68). This represents greater perfusi...

Diabetic nephropathy (DN), a leading cause of end-stage renal disease (ESRD), becomes a worldwide problem. Ultrastructural changes of the glomerular filtration barrier, especially the pathological changes of podocytes, lead to proteinuria in patients with diabetes. Podocytes are major components of glomerular filtration barrier, lining outside of the glomerular basement membrane (GBM) to mainta...