“Treasure your exceptions”: recent advances in molecular genetics of glomerular disease

Ciechanowicz, Andrzej; Brodkiewicz, Andrzej; Bińczak-Kuleta, Agnieszka; Parczewski, Miłosz; Czekalski, Stanisław

doi:10.1007/bf03195253

Cited by 2 publications

(2 citation statements)

References 27 publications

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“…By contrast, factors involved in the etiology of nephritic syndrome can vary, but may include circulating plate lets and white blood cells, the GBm, resident glomerular endothelial cells, and mesangial cells. 5 advances in our understanding of the molecular structure of glomeruli have revealed the major role of genetic defects in the development of glomerular diseases (Figure 1c-e). in this review, we focus on genetic abnormalities that affect the structural and functional integrity of the glomerulus.…”

Section: Introductionmentioning

confidence: 98%

Glomerular diseases: genetic causes and future therapeutics

Chiang

Inagi

2010

Nat Rev Nephrol

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The glomerulus consists of capillary tufts, a mesangial cell component and the Bowman capsule. The glomerular filtration barrier is composed of glomerular endothelial cells, a basement membrane, and podocytes. Particular components of the slit diaphragm and the glomerular basement membrane strictly orchestrate the integrity of the glomerular filtration barrier. The basement membrane is made of a highly crosslinked macromolecular meshwork of type IV collagen, proteoglycans, and laminin. Genetic forms of glomerular disease are predominantly caused by genetic defects in these molecular structures or in factors that regulate the glomerular filtration barrier. In addition, abnormal IgA1 glycosylation can increase susceptibility to IgA nephropathy. Dysregulation of the complement system or of platelet activation can lead to the development of endocapillary lesions, which manifest as thrombotic microangiopathy. Glomerular dysfunction is also encountered in several genetic metabolic and mitochondrial disorders. Discoveries of mutations in a range of genes have provided new insights into the mechanisms of glomerular disease. In this Review, we summarize recent progress in the genetics and therapeutics of a number of glomerular diseases.

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Section: Introductionmentioning

confidence: 98%

Glomerular diseases: genetic causes and future therapeutics

Chiang

Inagi

2010

Nat Rev Nephrol

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“…The slit diaphragm (SD) between interpodocyte foot processes (FPs) plays an important role in the glomerular filtration barrier to prevent proteins and other larger molecules from leaking to urine [2]. The identification of the SD molecules nephrin, podocin and CD2AP shed a new insight into the molecular mechanisms of proteinuria and the regulation of the glomerular filter [3]. Nephrin, the first identified SD protein, is a transmembrane adhesion protein of the immunoglobulin (Ig) superfamily and has been demonstrated to be a critical structural molecule of the SD.…”

Section: Introductionmentioning

confidence: 99%

Reduction in VEGF Protein and Phosphorylated Nephrin Associated with Proteinuria in Adriamycin Nephropathy Rats

Fan

Xing

Ding

et al. 2009

Nephron Exp Nephrol

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Background/Aims: The relationship between vascular endothelial growth factor (VEGF) and the phosphorylated critical podocyte slit diaphragm molecule nephrin is not fully clarified. This study investigated the dynamic changes in VEGF expression and nephrin phosphorylation, and the effects of the antiproteinuric drugs prednisone and lisinopril on them in Adriamycin nephropathy rats. Methods: Renal tissues from Adriamycin rats were collected at days 3, 7, 14, and 28. Distribution and expression of VEGF was revealed by immunohistochemistry, real-time PCR and Western blot. Phosphorylated nephrin was evaluated by immunoprecipitation. Results: A discontinuous redistribution of VEGF was displayed at day 3, followed by significant protein reduction at day 7 with persistent downregulation to day 28. Phosphorylated nephrin decreased evidently at day 14 and persisted to day 28. The reduction in VEGF and phosphorylated nephrin was not a result of podocyte loss. The intervention of prednisone and lisinopril evidently reduced proteinuria, effectively attenuated the severe lesions of podocyte foot processes, and restored the reduction in VEGF and nephrin phosphorylation. At day 28, the reduction in VEGF and phosphorylated nephrin was negatively correlated with proteinuria, whereas the phosphorylated nephrin was positively correlated with VEGF protein from day 7 to day 28. Conclusion: The reduction in VEGF protein and nephrin phosphorylation was possibly involved in the proteinuria in Adriamycin rats, and there might be some relationship between VEGF and nephrin phosphorylation. The antiproteinuric effects of lisinopril and prednisone were achieved at least partially by restoring VEGF protein and nephrin phosphorylation.

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“Treasure your exceptions”: recent advances in molecular genetics of glomerular disease

Cited by 2 publications

References 27 publications

Glomerular diseases: genetic causes and future therapeutics

Glomerular diseases: genetic causes and future therapeutics

Reduction in VEGF Protein and Phosphorylated Nephrin Associated with Proteinuria in Adriamycin Nephropathy Rats

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