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Hildebrandt's group has shown that 85% of the SRNS cases with onset by 3 months of age and 66% with onset by 1 year of age can be explained by recessive mutations in one of four genes only (NPHS1, NPHS2, LAMB2, or WT1).

WT+STZ mice showed increased kidney:body weight ratio due to cell hypertrophy, increased albuminuria, decreased kidney nephrin, podocin, and podocyte number and increased transforming growth factor-beta and laminin compared with WT mice.

Nephrin, podocin, and podocyte number and effacement were restored, and transforming growth factor-beta and laminin levels were decreased in TLR2-/-+ STZ mice kidneys versus WT+STZ.

Structural injury was observed in mothers and their pups as Bowman's capsule and tubular dilatation and increased expression of PCNA that were decreased following omega-3 supplementation added to down regulation of Wnt4, Pax2 gene and podocin expression.

Alterations in the expression of podocin, CD2AP and TLR/NF-kappaB were assessed by western blotting.

Umb also significantly ameliorated the renal histopathological alteration, and down-regulated the expression of epithelial-to-mesenchymal transition-related molecular markers podocin and CD2AP.

BACKGROUND: Although heme-oxygenase (HO) is cytoprotective, its effects on podocyte regulators like podocalyxin, podocin, CD2-associated protein (CD2AP) in renal dysfunction in N (omega)-nitro-l-arginine-methyl ester (l-NAME) hypertension are largely unclear.

Correspondingly, HA enhanced the aberrant expression of nephrin alongside other important regulators of podocyte like podocalyxin, podocin, and CD2AP, and improved renal function by reducing albuminuria/proteinuria, while increasing creatinine clearance.

CONCLUSIONS: HA improves renal function by attenuating histopathological lesions, suppressing inflammatory/oxidative mediators, abating profibrotic/extracellular matrix proteins, and reducing albuminuria/proteinuria, while concomitantly potentiating the HO-adiponectin-ANP axis, enhancing nephrin, podocin, podocalyxin, CD2AP and increasing creatinine clearance.

Decreased expression of nephrin and podocin and increased desmin-positive area in failing rats were restored by tolvaptan.

Cellular expressions of inflammation (CD14/CD68), DNA-damage (gamma-H2AX, CD90/XRCC1) and proximal-renal tubule (KIM-1) biomarkers displayed an identical pattern, whereas podocyte-integrity markers (podocin/ZO-1/p-cadherin/synaptopodin) showed a pattern opposite to that of creatinine level among all groups (all p < 0.001).

In all lines, the quantities of NEPH1 and podocin proteins and NEPH1 and SYNPO mRNAs were comparable to glomeruli, while synaptopodin and nephrin proteins and NPHS1 and NPHS2 mRNAs were <5% of glomerular levels.

In all lines, the quantities of NEPH1 and podocin proteins and NEPH1 and SYNPO mRNAs were comparable to glomeruli, while synaptopodin and nephrin proteins and NPHS1 and NPHS2 mRNAs were <5% of glomerular levels.

In all lines, the quantities of NEPH1 and podocin proteins and NEPH1 and SYNPO mRNAs were comparable to glomeruli, while synaptopodin and nephrin proteins and NPHS1 and NPHS2 mRNAs were <5% of glomerular levels.

Protein levels of nephrin, podocin, CD2-associated protein, and podocalyxin were investigated using quantitative immunohistochemical assays.

Real-time PCR was used to determine the mRNA levels of nephrin, podocin, and podoplanin in microdissected glomeruli.

In most acquired renal diseases, except in IgA nephropathy, a marked reduction was observed at the protein levels of nephrin, podocin, and podocalyxin, whereas an increase of the glomerular mRNA levels of nephrin, podocin, and podoplanin was found, compared with controls.

In most acquired renal diseases, except in IgA nephropathy, a marked reduction was observed at the protein levels of nephrin, podocin, and podocalyxin, whereas an increase of the glomerular mRNA levels of nephrin, podocin, and podoplanin was found, compared with controls.

To explore the significance of Sall1 in differentiated podocytes, we investigated podocyte-specific Sall1-deficient mice (Sall1 KO(p) degrees (d) degrees (/p) degrees (d) degrees ) using a podocin-Cre/loxP system and siRNA Sall1 knockdown (Sall1 KD) podocytes.

In the present study, the expression of TUG1, podocyte-specific markers (nephrin and podocin) and mitochondrial biogenesis-associated mRNAs (transcription factor A mitochondrial, cytochrome C oxidase subunit 5A and peroxisome proliferator-activated receptor gamma coactivator 1alpha) were examined in urinary sediment of non-diabetic patients with biopsy-confirmed glomerulonephritides and healthy controls.

The protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptosis (Bax/caspase-3/PARP), fibrosis (Smad3/TGF-ss) and inflammation (TNF-alpha/NF-kappaB/MMP-2) and kidney injury score displayed an opposite pattern, whereas the protein expressions of TMP2, endothelial-cell markers (CD31/eNOS) and podocyte integrity biomarkers (podocin/ZO-1/synaptopodin) exhibited an identical pattern of RBF among the groups (all p < 0.001).

This study demonstrates that the expression of the mesenchymal markers CD29 and CD44, the epithelial markers CD51 and ZO-1 and the podocyte markers CD2AP and NPHS2 can be induced in these cells via incubation with epidermal growth factor/platelet-derived growth factor BB and fibroblast growth factor 4/hepatocyte growth factor, respectively.

METHODS: Messenger RNA levels of nephrin, podocin, podocalyxin, synaptopodin, and alpha-actinin-4 were measured in the kidney tissue and urinary cells by real-time polymerase chain reaction.

After six months of immunosuppressive therapy, patients with PGs showed a significant reduction in the expression of podocin, podocalyxin, and alpha-actinin-4 compared with baseline (p<0.001).

Epidermal growth factor receptor and podocin predict nephropathy progression in type 2 diabetic patients through interaction with the autophagy influencer ULK-1.

Therefore, the aim of current study was to evaluate and correlate circulating levels of autophagy regulator protein Unc-51-like kinase 1 (ULK-1) with the widely expressed receptor in mammalian kidney; epidermal growth factor receptor (EGFR); and the key functional podocyte protein podocin (PDCN).

Therefore, the aim of current study was to evaluate and correlate circulating levels of autophagy regulator protein Unc-51-like kinase 1 (ULK-1) with the widely expressed receptor in mammalian kidney; epidermal growth factor receptor (EGFR); and the key functional podocyte protein podocin (PDCN).

RESULTS: Microalbuminuria and macroalbuminuria patients exhibited decreased ULK-1, EGFR and PDCN levels.

ULK-1, EGFR and PDCN were correlated with each other and with some metabolic parameters.

CONCLUSIONS: ULK-1 with EGFR can predict early impairment in DN while PDCN can highlight progressive DN risk EGFR and PDCN may interact synergistically with ULK-1 in autophagy dysregulation as a pathogenic mechanism of DN induction and progression.

CONCLUSIONS: ULK-1 with EGFR can predict early impairment in DN while PDCN can highlight progressive DN risk EGFR and PDCN may interact synergistically with ULK-1 in autophagy dysregulation as a pathogenic mechanism of DN induction and progression.

ASE improved biomarkers of renal filtration barrier (podocin and nephrin) in D and DH groups and prevented the increased expression of caspase-3, IL-6, TNF-alpha and MCP-1 in both groups.

The untreated prediabetic (PD) rats presented increased fluid intake and urine output; increased creatinine, urea, and uric acid plasma concentrations; albuminuria; proteinuria; sodium retention; potassium loss; increased aldosterone and kidney injury molecule (KIM-1) concentration; and increased urinary podocin mRNA expression.

However, BA administration attenuated the renal markers and oxidative stress and decreased the urinary podocin mRNA expression.

The urinary excretion of nephrin and podocin, two podocyte-specific markers, and WAP-four-disulfide core domain protein 2 (WFDC-2), a marker of tubulointerstitial fibrosis, was determined by ELISA in comparison with healthy controls.

Excretion of nephrin and podocin was increased in patients with albuminuria, regardless of decline in renal function (P < 0.001), correlating positively with UACR.

Podocyte stress (Urinary pellet podocin:nephrin mRNA ratio), podocyte detachment (Urinary pellet podocin mRNA:creatinine ratio: UPPod:CR) and a tubular marker (Urinary pellet aquaporin 2:creatinine ratio) were measured in macro-albuminuric, micro-albuminuric and norm-albuminuric groups. eGFR was reassessed after 4 years in 124 available diabetic subjects.

The quantification of the podocyte-associated mRNAs of alpha-actinin-4, podocin, and podocalyxin, as well as of the profibrotic factors TGF-beta1, CTGF, and VEGF-A were quantified by real-time polymerase chain reaction.

Tissue and urine mRNA of nephrin, podocin, podocalyxin, alpha-actinin-4, transient receptor potential cation channel 6, and of growth factors VEGF-A and TGF-beta1 and the transcription factor FOXP3 were measured using real time polymerase chain reaction.

METHODOLOGY/PRINCIPAL FINDINGS: Protein expression of synaptopodin, podocin and nephrin were quantified in 15 Type 2 diabetic renal biopsies and 12 control patients.

We found statistically significant downregulation of synaptopodin (P<0.0001), podocin (P = 0.0002), and nephrin (P<0.0001) in kidney biopsies of diabetic nephropathy as compared with controls.

Here, we describe already well-characterized genetic diseases due to mutations in nephrin, podocin, CD2AP, alpha-actinin-4, WT1, and laminin beta2 chain, as well as more recently identified genetic abnormalities in TRPC6, phospholipase C epsilon, and the proteins encoded by the mitochondrial genome.

METHODS: We quantified in urinary sediments of 32 SLE patients and 20 controls, mRNA and protein levels of podocalyxin, synapotopodin, podocin, nephrin and WT-1 by quantitative real-time polymerase chain reaction and western blot analysis and correlated these with clinical and histological parameters.

Absolute quantification of podocin, a potential biomarker of glomerular injury in human urine, by liquid chromatography-multiple reaction monitoring cubed mass spectrometry.

In this context, quantification of podocin could be of great interest since it is a protein exclusively present in highly specialized glomerulus cells called podocytes.

This paper describes the development of a quantification method of human podocin in urine by LC-MS/MS in MRM(3) mode.

Inter assay precision and accuracy ranged from 7 to 20% and from 105 to 112% respectively and the lower limit of quantification (LLOQ) was 0.39ng/mL from only 1mL of urine which is compatible for endogenous level of podocin determination.

The expression of regulator of calcineurin 1 and the podocin to nephrin ratio (PNR) were also increased in the PAN nephritis model.

Recently, identification of the mutated genes for some podocyte proteins (nephrin, podocin, alpha-actinin-4) in rare familial forms of nephrotic syndrome shed has new light on the molecular mechanisms of glomerular permselectivity.

Gradually it becomes apparent that sporadic mutations of podocyte proteins (e.g., podocin) may be present even in some patients with acquired nephrotic syndrome.

Our aim was to compare urinary excretion of podocin and podocalyxin, which are biomarkers of podocyte injury, and to assess their relationship with proteinuria and renal function in ADPKD.

Podocin, podocalyxin protein levels, and proteinuria were measured in urine.

RESULTS: Patients with ADPKD had higher podocin and podocalyxin levels compared to the control group.

The levels of podocin and podocalyxin were higher in ADPKD patients both with eGFR >/=60 mL/min/1.73 m2 and with eGFR <60 mL/min/1.73 m2 than in controls.

The levels of podocin and podocalyxin were higher in ADPKD patients with eGFR <60 mL/min/1.73 m2 than in ADPKD patients with eGFR >/=60 mL/min/1.73 m2.

Podocin and podocalyxin were negatively correlated with eGFR and positively correlated with urine protein to creatinine ratio in ADPKD patients.

Exosomes were found to contain many disease-associated proteins including aquaporin-2, polycystin-1, podocin, non-muscle myosin II, angiotensin-converting enzyme, Na+ K+ 2Cl- cotransporter (NKCC2), thiazide-sensitive Na-Cl cotransporter (NCC), and epithelial sodium channel (ENaC).

Transplanted CSC homed to glomeruli, where they expressed CR1, VEGFA, SYNAPTOPODIN, CD2AP, and PODOCIN at the RNA level and produced PODOCIN, CD2AP, and COLIValpha3 proteins in nontransplanted -/- mice, indicating that CSC have adopted a podocyte phenotype.

The expression of podocyte-specific proteins (podocalyxin, glomerular epithelial protein-1, podocin, nephrin, synaptopodin, and alpha-actinin-4), podocyte synthesized proteins (vascular endothelial growth factor and novH), transcription factors (WT1 and PAX2), cyclin-dependent kinase inhibitor p57, and intermediate filaments (cytokeratins and vimentin) was tested.

Podocin mRNA was absent from all eight clones.

On the cellular level--using immunostaining--we detected cells expressing podocin, nephrin and wt-1, characteristic for differentiated podocytes and other cells, which expressed Tamm-Horsfall protein, a marker for distal tubule epithelial cells of kidney tissue.

Hsf-1 affects podocyte markers NPHS1, NPHS2 and WT1 in a transgenic mouse model of TTRVal30Met-related amyloidosis.

MATERIALS AND METHODS: Immunohistochemistry, immunoblot and gene expression studies for nephrin, podocin and WT1 were run on renal tissue from human-TTRV30M transgenic mice hemizygous or homozygous for heat shock factor one (Hsf-1).

RESULTS: Glomeruli of hsf-1 hemizygous transgenic mice showed lower nephrin and podocin protein levels but an increased podocyte number when compared to Hsf-1 homozygous transgenic mice.

Nephrin, podocin and WT1 gene expression levels were unaffected by the Hsf-1 carrier status.

CONCLUSIONS: Under the effect of Hsf-1 hemizygosity, TTRV30M deposition has deleterious effects on GBM thickness, PFW and slit diaphragm composition, without affecting nephrin and podocin gene expression.

The urine sediments were analyzed for podocytes, identified by staining for podocin after culturing the urinary sediments for 24 hours.

The urine podocin/creatinine ratio as a novel biomarker of cardiorenal syndrome in dogs due to degenerative mitral valve disease.

NPHS1, PLCE1, NPHS2, and SMARCAL1 were the most common genes in which we detected a mutation.

MAIN OUTCOME MEASURED: Are the podocyte specific proteins, podocalyxin, podocin, nephrin and synaptopodin able to detect pre-eclampsia prior to the development of clinical signs as measured by two separate techniques.

RESULTS: The results suggest that the expression of podocyte specific proteins, podocalyxin, podocin, nephrin and synaptopodin, is identifiable and quantifiable from midstream urine in healthy normotensive pregnant women.

The mRNA abundance of 3 podocyte-specific markers in urinary sediment (nephrin, podocin and synaptopodin) was measured with real-time quantitative PCR.

All the subjects were categorized according to their urinary podocyte marker profile into 2 groups, those with only synaptopodin mRNA presence (synaptopodin only group) and those with nephrin and/or podocin mRNA presence in addition to synaptopodin in their urine (nephrin and/or podocin group).

All the subjects were categorized according to their urinary podocyte marker profile into 2 groups, those with only synaptopodin mRNA presence (synaptopodin only group) and those with nephrin and/or podocin mRNA presence in addition to synaptopodin in their urine (nephrin and/or podocin group).

The presence of nephrin and/or podocin mRNA in urine was more frequent among DM patients compared to controls (53.5 vs. 30.8%, respectively; p = 0.022).

Binary logistic regression analysis revealed that the only significant predictor of the presence of nephrin and/or podocin mRNA in urine was the presence of DM (OR 2.59, 95% CI 1.14-5.91, p = 0.024, adjusted for all risk factors).

A strong correlation between nephrin and podocin urinary mRNA levels was noted (r = +0.796, p < 0.001).

DM is the only significant determinant of the presence of nephrin and/or podocin mRNA in urine in this population.

The GMV fraction was composed of podocin/podocalyxin-positive irregularly shaped membranous vesicles and podocin/podocalyxin-negative classical exosomes.

Treatment with PAL also restored podocin expression and reduced inflammation markers such as intracellular adhesion molecules (ICAM-1), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor alpha (TNF-alpha) and high-mobility group box-1 (HMGB1).

Genetic forms of INS, with mutation of the NPHS1 and NPHS2 genes encoding nephrin and podocin, are mostly steroid resistant and very rarely recur in the transplant.

Genetic forms of INS, with mutation of the NPHS1 and NPHS2 genes encoding nephrin and podocin, are mostly steroid resistant and very rarely recur in the transplant.

Genetic forms of INS, with mutation of the NPHS1 and NPHS2 genes encoding nephrin and podocin, are mostly steroid resistant and very rarely recur in the transplant.

The expression of podocyte molecules (WT1, nephrin, podocin, alpha-actinin 4 and CD2AP) were also investigated in a renal specimen of this FS patient.

Most of these cells exhibited endothelial phenotypes, being negative for several markers, including podocin (a maker of podocyte), alpha8 integrin (mesangial cell), CD68, and F4/80 (macrophage).

Relative mRNA abundance of nephrin, podocalyxin, and podocin were quantified, and correlations between target mRNAs and clinical parameters were examined.

The expression of nephrin, podocalyxin, and podocin mRNA correlated with serum creatinine {(r=0.397, p value=0.002), (r=0.431, p value=0.001), (r=0.433, p value=0.001) respectively}.

CONCLUSION: The urinary mRNA profiles of nephrin, podocalyxin, and podocin were found to increase with the progression of DN, which suggested that quantification of podocyte-associated molecules will be useful biomarkers of DN.

One half of the sediment was cultured for 24 h to select for viable cells and then stained with a podocin antibody, followed by a secondary fluorescein isothiocyanate-labeled antibody to identify podocytes.

podocin-specific

In the respective samples, the presence of a podocin-specific tryptic peptide was confirmed with LC-MS/MS technology.

Calcitriol, a bioactive 1,25-dihydroxyvitamin D3, ameliorated proteinuria and renal damage as well as reversed the decline of both nephrin and podocin, crucial structural proteins in podocytes.

Furthermore, the protein expression of inducible nitric oxide synthase, a crucial marker of M1 macrophages, was negatively correlated with the expression of either nephrin or podocin, whereas CD163, indicating M2 macrophages, was positively correlated.

Urinary DPP4 correlates with renal dysfunction, and DPP4 inhibition protects against the reduction in megalin and podocin expression in experimental CKD.

Higher levels of proteinuria in Nx rats compared to control rats were accompanied by higher urinary excretion of retinol-binding protein 4, a marker of tubular proteinuria, as well as higher urinary levels of podocin, a marker of glomerular proteinuria.

Retinol-binding protein 4 and podocin were not detected in the urine of Nx + DPP4i rats.

Tubular and glomerular proteinuria was associated with the reduced expression of megalin and podocin in the renal cortex of Nx rats.

Collectively, these results suggest that DPP4 inhibition ameliorated both tubular and glomerular proteinuria and prevented the reduction of megalin and podocin expression in CKD rats.

Mutations in nephrin (NPHS1), podocin (NPHS2), laminin beta2 (LAMB2), and alpha-actinin-4 (ACTN4) have been shown to induce ER stress in HEK293 cells and podocytes in hereditary nephrotic syndromes; various founder mutations in collagen IV alpha chains (COL4A) have been demonstrated to activate podocyte ER stress in collagen IV nephropathies; and mutations in uromodulin (UMOD) have been reported to trigger tubular ER stress in autosomal dominant tubulointerstitial kidney disease.

Mutations in nephrin (NPHS1), podocin (NPHS2), laminin beta2 (LAMB2), and alpha-actinin-4 (ACTN4) have been shown to induce ER stress in HEK293 cells and podocytes in hereditary nephrotic syndromes; various founder mutations in collagen IV alpha chains (COL4A) have been demonstrated to activate podocyte ER stress in collagen IV nephropathies; and mutations in uromodulin (UMOD) have been reported to trigger tubular ER stress in autosomal dominant tubulointerstitial kidney disease.