Podocyte is the major culprit accounting for the progression of chronic renal disease

Kriz, Wilhelm

doi:10.1002/jemt.10072

Cited by 160 publications

(128 citation statements)

References 36 publications

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“…Accumulating evidence emphasizes an essential role of podocyte injury in proteinuria (25,26). This model is characterized by heavy proteinuria with eventual hypoproteinemia and hyperlipidemia.…”

Section: Discussionmentioning

confidence: 99%

Novel Serpinopathy in Rat Kidney and Pancreas Induced by Overexpression of Megsin

Inagi

Nangaku²,

Usuda³

et al. 2005

Journal of the American Society of Nephrology

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The intracellular polymerization of abnormal serine protease inhibitors (serpins) results in liver or neuronal cell abnormalities recently identified as "serpinopathies." It was demonstrated in transgenic rats that overexpression of megsin, a recently discovered serpin located in the kidney, produces renal and pancreatic lesions characteristic of serpinopathies. Megsin expression is elevated in a variety of organs, including kidney and pancreas. Periodic acid-Schiff-positive, diastase-resistant intracellular inclusions develop only in the kidney and the pancreas. They correspond to electron-dense deposits, shown to contain megsin by immunohistochemistry and immunoelectron microscopy. In the kidney, inclusions are located mainly in the endoplasmic reticulum of glomerular epithelial, distal, and collecting duct cells, and are associated with massive proteinuria and an impaired renal function. In the pancreas, similar inclusions are found in the exocrine and Langerhans islet cells, where islet ␤ cells are reduced as a result of apoptosis. They are associated with diabetes with low insulin levels. The animals have an impaired growth and die within 10 wk. Rats that overexpress a mutant megsin, characterized by a deficient conformational transition activity, do not develop the serpinopathy, suggesting that some conformational flexibility of the serpin is required for the development of serpinopathy. This model of serpinopathy is the first to involve the kidney and the pancreas.

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Section: Discussionmentioning

confidence: 99%

Novel Serpinopathy in Rat Kidney and Pancreas Induced by Overexpression of Megsin

Inagi

Nangaku²,

Usuda³

et al. 2005

Journal of the American Society of Nephrology

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“…We also performed in vitro and in vivo experiments to address the functional relevance of NADPH oxidase-mediated triggering of NALP3 inflammasomes on Hcys-stimulated podocyte and glomerular injury. Podocytes, the epithelial cells lining the outermost layer of the glomeruli, are essential for proper filtration, and injury to podocytes is indicative of impaired glomerular filtration, in time leading to glomerular sclerosis (13,15). Foot process effacement, considered as the hallmark sign of podocyte injury, is usually accompanied by the destruction of the actin cytoskeleton, increased expression of slit diaphragm molecule and podocyte injury factor desmin, and reduction of the slit diaphragm molecule podocin, which is important for cell polarity and survival.…”

Section: Nadph Oxidase and Inflammasome Activation In Podocytesmentioning

confidence: 99%

NADPH Oxidase-Mediated Triggering of Inflammasome Activation in Mouse Podocytes and Glomeruli During Hyperhomocysteinemia

Abais

Zhang

Xia

et al. 2013

Antioxidants & Redox Signaling

130

136

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Aim: Our previous studies have shown that NOD-like receptor protein (NALP3) inflammasome activation is importantly involved in podocyte dysfunction and glomerular sclerosis induced by hyperhomocysteinemia (hHcys). The present study was designed to test whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated redox signaling contributes to homocysteine (Hcys)-induced activation of NALP3 inflammasomes, an intracellular inflammatory machinery in podocytes in vitro and in vivo. Results: In vitro confocal microscopy and size-exclusion chromatography revealed that upon NADPH oxidase inhibition by gp91 phox siRNA, gp91ds-tat peptide, diphenyleneiodonium, or apocynin, aggregation of inflammasome proteins NALP3, apoptosis-associated speck-like protein (ASC), and caspase-1 was significantly attenuated in mouse podocytes. This NADPH oxidase inhibition also resulted in diminished Hcys-induced inflammasome activation, evidenced by reduced caspase-1 activity and interleukin-1b production. Similar findings were observed in vivo where gp91phox -/ -mice and mice receiving a gp91ds-tat treatment exhibited markedly reduced inflammasome formation and activation. Further, in vivo NADPH oxidase inhibition protected the glomeruli and podocytes from hHcys-induced injury as shown by attenuated proteinuria, albuminuria, and glomerular sclerotic changes. This might be attributed to the fact that gp91phox -/ -and gp91ds-tat-treated mice had abolished infiltration of macrophages and T-cells into the glomeruli during hHcys. Innovation: Our study for the first time links NADPH oxidase to the formation and activation of NALP3 inflammasomes in podocytes. Conclusion: Hcys-induced NADPH oxidase activation is importantly involved in the switching on of NALP3 inflammasomes within podocytes, which leads to the downstream recruitment of immune cells, ultimately resulting in glomerular injury and sclerosis. Antioxid. Redox Signal. 18, 1537-1548.

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“…[1][2][3] The podocyte is the primary target of injury in several immunologic and nonimmunologic forms of glomerulonephritis. 4,5 Podocyte loss and the determination of urinary messenger RNA (mRNA) levels have been shown to be an important component of the progression of glomerular diseases.…”

Section: Introductionmentioning

confidence: 99%

Relationship between Urinary Podocytes and Kidney Diseases

Sun

Zhao

Li³

2012

Renal Failure

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Podocyte loss is an important component of disease progression in glomerular diseases. To some extent, the loss of podocytes can predict the degree of damage and the advancement of renal disease. Detecting the loss of podocytes in the urine could be a valuable, noninvasive method for obtaining information about the activity of the disease or the disease type, allowing the early diagnosis of glomerular diseases. One of the most robust markers that has been successfully used for urinary podocyte diagnostics is podocalyxin (PDX). PDX is a sialoprotein that is expressed on podocytes and on a variety of nonrenal cells as well as on glomerular endothelial and parietal epithelial cells. Therefore, podocyte loss can be detected by the amount of PDX in the urine. The relationship between urinary podocytes and renal diseases is supported by the detection of podocytes in patients with immunoglobulin A (IgA) nephropathy, HenochSchönlein purpura nephritis, lupus nephritis, diabetic nephropathy, and focal segmental glomerulosclerosis. The use of technology for detecting podocytes in the urine would have broad implications for the evaluation of disease activity, the degree of dedifferentiation, and the possibility of regeneration.

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Podocyte is the major culprit accounting for the progression of chronic renal disease

Cited by 160 publications

References 36 publications

Novel Serpinopathy in Rat Kidney and Pancreas Induced by Overexpression of Megsin

Novel Serpinopathy in Rat Kidney and Pancreas Induced by Overexpression of Megsin

NADPH Oxidase-Mediated Triggering of Inflammasome Activation in Mouse Podocytes and Glomeruli During Hyperhomocysteinemia

Relationship between Urinary Podocytes and Kidney Diseases

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