Disease relevance of Podocytes

• Our results provide the first example of an essential role for a sialomucin in development and suggest that defects in podocalyxin could play a role in podocyte dysfunction in renal failure and omphalocele in humans [1].
• In summary, upregulation of B7-1 in podocytes may contribute to the pathogenesis of proteinuria by disrupting the glomerular filter and provides a novel molecular target to tackle proteinuric kidney diseases [2].
• Induction of B7-1 in podocytes is associated with nephrotic syndrome [2].
• Basic fibroblast growth factor augments podocyte injury and induces glomerulosclerosis in rats with experimental membranous nephropathy [3].
• B7-1 in podocytes was found in genetic, drug-induced, immune-mediated, and bacterial toxin-induced experimental kidney diseases with nephrotic syndrome [2].

High impact information on Podocytes

• Nck links nephrin to actin in kidney podocytes [4].
• Two papers, one in Nature (Jones et al., 2006) and the other in the Journal of Clinical Investigation (Verma et al., 2006) show that Nck adaptor proteins connect phosphorylated nephrin with actin polymerization in podocyte foot processes, structures important for slit-diaphragm formation in the kidney [4].
• Here, we show that the canonical transient receptor potential 6 (TRPC6) ion channel is expressed in podocytes and is a component of the glomerular slit diaphragm [5].
• NPHS2 is almost exclusively expressed in the podocytes of fetal and mature kidney glomeruli, and encodes a new integral membrane protein, podocin, belonging to the stomatin protein family [6].
• Microheterogeneity of protein and sterol content in kidney podocyte membrane [7].

Chemical compound and disease context of Podocytes

• We generated podocin-deficient (Nphs2-/-) mice to investigate the function of podocin, a protein expressed at the insertion of the slit diaphragm in podocytes and defective in a subset of patients with steroid-resistant nephrotic syndrome and focal and segmental glomerulosclerosis [8].
• The discovery of the genes for nephrin and podocin, which are mutated in two types of congenital nephrotic syndrome, was pivotal in establishing the podocyte as the central component of the glomerular filtration barrier [9].
• Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy [10].
• CHOP was weakly expressed in podocytes of control kidneys but up-regulated in most proteinuric human kidneys and in rat puromycin nephrosis [11].
• The nephritogenic antigen of Heymann nephritis (HN)--a well-studied experimental rat model disease of human membranous glomerulonephritis (MGN)--was recently shown to be a 330-kd glycoprotein (gp330) which is present in the membranes of both the rat tubular brush borders and of podocytes [12].

Biological context of Podocytes

• Apoptosis in podocytes induced by TGF-beta and Smad7 [13].
• Altered podocyte structure in GLEPP1 (Ptpro)-deficient mice associated with hypertension and low glomerular filtration rate [14].
• Gene silencing of Synpo-T abrogates stress-fiber formation in synpo(-/-) podocytes, demonstrating that Synpo-T serves as a backup for Synpo-long in synpo(-/-) podocytes [15].
• In addition to expression in glomerular podocytes, the reporter gene was expressed in the brain and pancreas of (+/-) and (-/-) mice [16].
• A WT1 co-regulator controls podocyte phenotype by shuttling between adhesion structures and nucleus [17].

Anatomical context of Podocytes

• The distribution of podoendin is restricted to the surface of glomerular podocytes, urinary surface of the parietal epithelium of Bowman's capsule, and the luminal surface of endothelial cells [18].
• PCLP has been shown previously to be expressed on the foot processes of podocytes in the kidney glomerulus as well as on vascular endothelium at some sites [19].
• Podocalyxin is a CD34-related sialomucin that is expressed at high levels by podocytes, and also by mesothelial cells, vascular endothelia, platelets, and hematopoietic stem cells [1].
• Synaptopodin is the founding member of a novel class of proline-rich actin-associated proteins highly expressed in telencephalic dendrites and renal podocytes [15].
• Synaptopodin is an actin-associated protein of differentiated podocytes that also occurs as part of the actin cytoskeleton of postsynaptic densities (PSD) and associated dendritic spines in a subpopulation of exclusively telencephalic synapses [20].

Associations of Podocytes with chemical compounds

• Angiotensin II depolarizes podocytes in the intact glomerulus of the Rat [21].
• Our results suggest that Ang II depolarizes podocytes directly by opening a Cl- conductance [21].
• Glomerular visceral epithelial cells are endowed with a sialic acid-rich surface coat (the "glomerular epithelial polyanion"), which in rat tissue contains the sialoprotein podocalyxin [22].
• Glomerular epithelial protein 1 (GLEPP1) is a receptor tyrosine phosphatase present on the apical cell surface of the glomerular podocyte [14].
• It is also highly homologous in its transmembrane/intracellular domain to podocalyxinlike protein-1, a rabbit cell surface glycoprotein of kidney podocytes [23].

Gene context of Podocytes

• These data support the conclusion that the GLEPP1 (Ptpro) receptor plays a role in regulating the glomerular pressure/filtration rate relationship through an effect on podocyte structure and function [14].
• Transcriptional induction of slit diaphragm genes by Lmx1b is required in podocyte differentiation [24].
• TGF-beta1 and Smad7 each induce apoptosis in podocytes, and their coexpression has an additive effect [13].
• The finding that this disease is caused by mutations in the transcription factor LMX1B, which in the kidney is expressed exclusively in podocytes, offers the opportunity for a better understanding of the renal pathogenesis [25].
• For the earliest podocyte marker identified, Foxc2, knockout mice were used to analyze the role of this protein during glomerular development [26].

Analytical, diagnostic and therapeutic context of Podocytes

• Scanning and transmission electron microscopy showed that Ptpro(-/-) mice had an amoeboid rather than the typical octopoid structure seen in the wild-type mouse podocyte and that there were blunting and widening of the minor (foot) processes in association with altered distribution of the podocyte intermediate cytoskeletal protein vimentin [14].
• Electron microscopy demonstrated NEPH1 expression in glomerular podocytes and revealed effacement of podocyte foot processes in Neph1(-/-) mice [27].
• In the present study, the fate of Wt1 mutant cells in chimeric kidneys was assessed by in situ marker analysis, and immunocytochemistry was used to re-examine the claim that glomerulosclerosis (GS) is caused by loss of WT1 and persistent Pax-2 expression by podocytes [28].
• Here we demonstrate that CD2AP localizes to the slit diaphragm in podocytes using immunoelectron microscopy and that nephrin and CD2AP co-immunoprecipitate from a podocyte cell line [29].
• In situ hybridization demonstrated WTIP expression in developing E15 glomeruli and in cultured podocytes [17].

References