Adipokines have been reported to contribute to glomerular injury during obesity or diabetes mellitus. However, the mechanisms mediating the actions of various adipokines on the kidney remained elusive. The present study was performed to determine whether acid sphingomyelinase (ASM)-ceramide associated lipid raft (LR) clustering is involved in local oxidative stress in glomerular endothelial cel...

Primary defects in either podocytes or the glomerular basement membrane (GBM) cause proteinuria, a fact that complicates defining the barrier to albumin. Laminin beta2 (LAMB2) is a GBM component required for proper functioning of the glomerular filtration barrier. To investigate the GBM's role in glomerular filtration, we characterized GBM and overlying podocyte architecture in relation to deve...

Idiopathic NS (nephrotic syndrome) is characterized by massive proteinuria, due to a leak in the glomerular barrier to proteins. Genetic defects that affect the function and the composition of the glomerular capillary wall, in particular of the visceral epithelial cells, have recently been recognized as the cause of familial forms of NS. MCNS (minimal change NS) and FSGS (focal and segmental gl...

BACKGROUND The putative humoral mediator thought to be involved in the pathogenesis of idiopathic nephrotic syndrome has not yet been identified. However, components exist in normal serum that block the permeability activity of FSGS serum in vitro. The potential of FSGS serum to increase glomerular albumin permeability may result from an imbalance between permeability factors and naturally occu...

Most of the interest in the glomerular basement membrane (GBM) stems from the observation that it undergoes morphological changes in renal disease. Studies on persistent proteinuria in experimental animal models have shown that the permeability properties of the GBM have been altered as a result of protein degradation and cross-linking of type IV collagen via its NC1 domains promoted by reactiv...

AIM We have previously found that chronic endothelin-1 (ET-1) infusion in Sprague-Dawley rats increases glomerular permeability to albumin (P(alb)) as assessed in vitro independent of blood pressure with no observed albuminuria. In this study, we hypothesized that ET-1 increases glomerular albumin filtration with accompanied increase in albumin uptake via the proximal tubule, which masks the ex...

The glomerular basement membrane (GBM) is an important component of the filtration barrier that is the glomerular capillary wall. Previously GBM permeability has been investigated only under static pressures and often within a supraphysiological range. We used Matrigel as a model of GBM and formed membranes at the base of a filtration chamber. We measured membrane permeability under static and ...

Glomerular hemodynamics were studied by micropuncture technique in the unclipped kidney in rats in which modest two kidney Goldblatt hypertension was maintained for 4 weeks and in normotensive controls. Both groups ingested less than 2 mEq Na+/day. In hypertensive rats at micropuncture, mean hydrostatic pressure was elevated both systematically (128 +/- 5 vs 113 +/- 3 mm Hg, p less than 0.05) a...

A glomerular permeability defect occurs early in the course of type 1 diabetes and precedes the onset of microalbuminuria and renal morphological changes. Recently, ACE inhibitors have been shown to prevent loss of glomerular membrane permselective function, but the mechanism of this nephroprotective effect is still being debated. The objective of the present study was to evaluate the effects o...

Selective endothelin A (ET(A)) and combined ET(A) and ET(B) receptor antagonists are being investigated for use in treating diabetic nephropathy. However, the receptor-specific mechanisms responsible for producing the potential benefits have not been discerned. Thus, we determined the actions of ET(A) and ET(B) receptors on measures of glomerular function and renal inflammation in the early sta...