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OBJECTIVE A multicenter, controlled trial showed that early blockade of the renin-angiotensin system in patients with type 1 diabetes and normoalbuminuria did not retard the progression of nephropathy, suggesting that other mechanism(s) are involved in the pathogenesis of early diabetic nephropathy (diabetic nephropathy). We have previously demonstrated(More)
Calcium phosphate (CaP) based approaches remain an attractive option for delivering plasmid DNA (pDNA) into cultured cells. However, despite their appeal, current synthesis methodologies typically yield lower, less consistent transfection efficiencies when compared to viral approaches. Therefore, we report here a novel method to consistently synthesize(More)
TGF-beta is a key mediator in renal fibrosis. Kidney-targeted gene therapy with anti-TGF-beta strategies is expected to have therapeutic potential, but this has been hampered by concerns over the safety and practicability of viral vectors and the inefficiency of nonviral transfection techniques. The present study explored the potential role of TGF-beta/Smad(More)
Previous studies have reported that uric acid stimulates vascular smooth muscle cell (VSMC) proliferation in vitro. We hypothesized that uric acid may also have direct proinflammatory effects on VSMCs. Crystal- and endotoxin-free uric acid was found to increase VSMC monocyte chemoattractant protein-1 (MCP-1) expression in a time- and dose-dependent manner,(More)
Transforming growth factor-beta1 (TGF-beta1) promotes tissue fibrosis through the Smad3 signaling pathway. While phosphorylation is known to regulate Smad3 function, recent in vitro studies have suggested that acetylation may also regulate Smad3 function. This study investigated Smad3 acetylation in renal fibrosis. TGF-beta1 stimulation of renal fibroblasts(More)
Podocyte depletion plays a major role in the development and progression of glomerulosclerosis. Many kidney diseases are more common in older age and often coexist with hypertension. We hypothesized that podocyte depletion develops in association with older age and is exacerbated by hypertension. Kidneys from 19 adult Caucasian American males without overt(More)
Increases in glomerular size occur with normal body growth and in many pathologic conditions. In this study, we determined associations between glomerular size and numbers of glomerular resident cells, with a particular focus on podocytes. Kidneys from 16 male Caucasian-Americans without overt renal disease, including 4 children (≤3 years old) to define(More)
The podocyte depletion hypothesis has emerged as a unifying concept in glomerular pathology. According to this hypothesis podocyte depletion may be absolute (decrease in number of healthy mature podocytes), relative (fewer podocytes per unit of glomerular volume) or involve alterations to the specialized podocyte architecture (such as foot process(More)
Diabetic nephropathy is the leading cause of chronic renal failure. Myofibroblasts play a major role in the synthesis and secretion of extracellular matrix in diabetic renal fibrosis. Increasing evidence suggests that endothelial cells may undergo endothelial-myofibroblast transition under physiological and pathophysiological circumstances. Therefore, this(More)
Endothelial dysfunction and enhanced transforming growth factor-β (TGF-β)/Smad3 signalling are common features of progressive renal fibrosis. This study investigated a potential link between these mechanisms. In unilateral ureteric obstruction (UUO) we observed an acute (6 hr) down-regulation of nitric oxide synthase 3 (NOS3/eNOS) levels and increased(More)