Disease relevance of Nphs2

• Podocin is identified as a product of the gene mutated in a patient with autosomal recessive steroid-resistant nephrotic syndrome [1].
• Decreased mRNA expression of nephrin and podocin was observed before the onset of proteinuria [2].
• CONCLUSION: Nephrin is dissociated from podocin and excreted into urine in the early stages of Heymann nephritis [2].
• Decreased expression levels of the glomerular slit membrane proteins, nephrin and podocin, have been reported after the onset of puromycin aminonucleoside (PA) nephrosis [3].
• However, the first change induced by PA was the change of podocin localization from a linear pattern to a dot-like one prior to the onset of albuminuria [3].

High impact information on Nphs2

• SRC-family kinase Fyn phosphorylates the cytoplasmic domain of nephrin and modulates its interaction with podocin [4].
• In summary, Fyn phosphorylates the cytoplasmic domain of nephrin on tyrosine, leading to enhanced association with podocin and downstream signaling of nephrin [4].
• Podocin staining was restricted to the basal side of the podocyte of the early developing stage, whereas nephrin staining was detected on the basolateral surface of podocyte [1].
• Amino acid sequences of rat and human podocin are highly homologous (84.3% identity) [1].
• The mRNA expression for podocin was detected in glomeruli and the nerve tissues [1].

Chemical compound and disease context of Nphs2

• METHODS: The expression and the localization of slit diaphragm-associated molecules (nephrin, podocin, and CD2AP) and other podocyte-associated molecules (podocalyxin and alpha(3) integrin) in passive and active Heymann nephritis were analyzed by immunofluorescence and Western blot analysis [2].
• Proteinuria and glomerular nephrin and podocin immunofluorescence were examined in rat kidneys with adriamycin-induced NS and the effects of antiproteinuric drug therapies during 5 wk with enalapril, losartan, alone or in combination, omapatrilat, and mycophenolate mofetil on these parameters were assessed [5].
• Nephrin and podocin expression around the onset of puromycin aminonucleoside nephrosis [3].

Biological context of Nphs2

• Notably, gene expressions of podocyte-associated molecules nephrin and podocin were markedly decreased in aldosterone-infused rats at 2 weeks, with a gradual decrease thereafter [6].
• The results showed diminished protein levels of podocin and nephrin in the PA-treated group. beta-catenin showed distinct down-regulation at 3 days of induction, and the control level was reached at 10 days. beta1 integrin was markedly up-regulated during induction. alpha-actinin-4 was not changed at the studied time points [7].

Anatomical context of Nphs2

• Podocin is observed at the site of tight junction newly formed in proteinuric state in PAN nephropathy [1].

Associations of Nphs2 with chemical compounds

• The redistribution of podocin paralleled with nephrin in ANA nephropathy but not in PAN nephropathy [1].
• Enalapril alone or in combination with losartan resulted in significant preservation of podocin [5].
• The molecules studied included the filtration slit component nephrin, the hairpin-like membrane protein podocin, the basolateral adhesion molecules beta1 integrin and alpha-dystroglycan, and the cytoskeleton-linking intermediary beta-catenin and the actin-associated alpha-actinin-4 [7].

Regulatory relationships of Nphs2

• Fyn also significantly augmented the activation of the AP-1 promoter induced by nephrin and podocin [4].

Other interactions of Nphs2

• RESULTS: Cells obtained in the urine from PHN rats were positive for synaptopodin, nephrin, podocin, WT-1, and GLEPP1 (podocyte-specific antigens) [8].
• All cells from diabetic rats stained positive for the podocyte-specific proteins synaptopodin, nephrin, podocin and Glepp-1 and negative for mesangial (OX-7), tubular (Tamm-Horsfall protein) and endothelial (RECA) cell antigens [9].
• When proteinuria disappeared, podocin recovered whereas nephrin did not (P = 0.02); alpha-actinin intensity increased (P = 0.009) and the distribution changed [10].

Analytical, diagnostic and therapeutic context of Nphs2

• The mRNA levels of nephrin and podocin in whole kidney total RNA were quantified by the TaqMan real time PCR quantification system [3].

References