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Mutations of NPHS1 or NPHS2, the genes encoding nephrin and podocin, as well as the targeted disruption of CD2-associated protein (CD2AP), lead to heavy proteinuria, suggesting that all three proteins are essential for the integrity of glomerular podocytes, the visceral glomerular epithelial cells of the kidney. It has been speculated that these proteins(More)
Injury and loss of podocytes are leading factors of glomerular disease and renal failure. The postmitotic podocyte is the primary glomerular target for toxic, immune, metabolic, and oxidant stress, but little is known about how this cell type copes with stress. Recently, autophagy has been identified as a major pathway that delivers damaged proteins and(More)
Mutations of NPHS1 or NPHS2, the genes encoding for the glomerular podocyte proteins nephrin and podocin, cause steroid-resistant proteinuria. In addition, mice lacking NEPH1 develop a nephrotic syndrome that resembles NPHS mutations, suggesting that all three proteins are essential for the integrity of glomerular podocytes. Podocin interacts with the(More)
The assembly of specific synaptic connections represents a prime example of cellular recognition. Members of the Ig superfamily are among the most ancient proteins represented in the genomes of both mammalian and invertebrate organisms, where they constitute a trans-synaptic adhesion system. The correct connectivity patterns of the highly conserved(More)
Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular diagnosis resulting in end-stage renal disease. Defects in several podocyte proteins have been implicated in the etiology of FSGS, including podocin, alpha-actinin-4, CD2-associated protein (CD2AP), and TRPC6. Despite our growing understanding of genes involved in the(More)
Neuroendocrine chromaffin cells exist in both intra- and extra-adrenal locations; the organ of Zuckerkandl (OZ) constitutes the largest accumulation of extra-adrenal chromaffin tissue in mammals. The OZ disappears postnatally by modes that are still enigmatic but can be maintained by treatment with glucocorticoids (GC). Whether the response to GC reflects a(More)
Podocyte injury is a central mechanism in the pathogenesis of proteinuria. Prostaglandin E 2 (PGE 2) has been suggested to protect podocytes from cellular injury. Here we investigated whether PGE 2-induced gene expression accounts for the protective role of PGE 2 in podocytes. Using a suppressive-subtractive hybridization method, we isolated a(More)
Epigenetic mechanisms are fundamental key features of developing cells connecting developmental regulatory factors to chromatin modification. Changes in the environment during renal development can have long-lasting effects on the permanent tissue structure and the level of expression of important functional genes. These changes are believed to contribute(More)
Mutations in the gene NPHS2 are the most common cause of hereditary steroid-resistant nephrotic syndrome. Its gene product, the stomatin family member protein podocin represents a core component of the slit diaphragm, a unique structure that bridges the space between adjacent podocyte foot processes in the kidney glomerulus. Dislocation and misexpression of(More)
Chronic kidney disease (CKD) represents a major health burden. Its central feature of renal fibrosis is not well understood. By exome sequencing, we identified mutations in FAN1 as a cause of karyomegalic interstitial nephritis (KIN), a disorder that serves as a model for renal fibrosis. Renal histology in KIN is indistinguishable from that of(More)