Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Glomerular microRNA data of the kidney podocyte-specific cyclin-G associated kinase (Gak) deficient mice

ABSTRACT: Evidence for reduced expression of cyclin-G associated kinase (GAK) in glomeruli of chronic kidney disease patients was observed in the Nephroseq human database and was found to be associated with the decline in kidney function. To examine the role of GAK, a protein that functions to uncoat clathrin during endocytosis, we generated podocyte-specific Gak knockout mice (Gak KO) which developed progressive proteinuria and kidney failure with global glomerulosclerosis. We isolated glomeruli from the mutant mice to perform messenger RNA profiling and unearthed evidence for dysregulated podocyte calpain protease activity as an important contributor to this process. Treatment with calpain inhibitor III specifically inhibited calpain-1/-2 activities, mitigated the degree of proteinuria and glomerulosclerosis, and led to a striking increase in survival in the Gak KO mice. Podocyte-specific deletion of Capns1, essential for calpain-1 and calpain-2 activities, also improved proteinuria and glomerulosclerosis in Gak KO mice. Increased podocyte calpain activity mediated proteolysis of IkB resulted in increased NF-kBp65 induced Gadd45b expression in the Gak KO mice. Our results suggest that loss of podocyte associated Gak induces glomerular injury secondary to calcium dysregulation and aberrant calpain activation, which when inhibited, can provide a protective role.

ORGANISM(S): Mus musculus

PROVIDER: GSE158384 | GEO | 2020/12/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

RNA-seq analysis using glomeruli isolated from control and podocyte-specific bPIX deficient mice

Project description:We found that podocyte-specific bPIX deficient (KO) mice developed progressive proteinuria starting at ~8 weeks of age, and glomerulosclerosis and podocyte loss by 13 weeks of age. To investigate the mechanism of podocyte loss induced by bPIX deficiency, we analyzed mRNA expression by RNA-sequence using isolated glomeruli from control (CTRL) and KO mice.

2019-10-12 | GSE138774 | GEO

Human iPSC-derived glomeruli provide an advanced model to interrogate podocyte biology and accurately recapitulate podocytopathy

Project description:Podocytes are highly specialised cells within the glomeruli of the kidney that maintain the filtration barrier by forming interdigitating foot processes and slit-diaphragms. Disruption to these features result in proteinuria and glomerulosclerosis. Studies into podocyte biology and disease have previously relied on conditionally immortalised cell lines due to the non- proliferative nature of this cell type. Here we describe an advanced model to study both podocyte and glomerular biology using isolated glomeruli from kidney organoids derived from human pluripotent stem cells.

2018-12-04 | GSE111992 | GEO

Podocyte-specific deletion of tubular sclerosis complex 2 causes focal segmental glomerular sclerosis and progressive renal failure

Project description:Obesity can initiate and accelerate the progression of kidney diseases. However, it remains unclear how obesity affects renal dysfunction. Here, we show that a newly generated podocyte-specific tubular sclerosis complex 2 (Tsc2) knockout mouse model (Tsc2∆podocyte) develops proteinuria and dies due to end-stage renal dysfunction by 10 weeks of age. Tsc2∆podocyte mice exhibit an increased glomerular size and focal segmental glomerulosclerosis, including podocyte foot process effacement, mesangial sclerosis and proteinaceous casts. Podocytes isolated from Tsc2∆podocyte mice show nuclear factor, erythroid derived 2, like 2-mediated increased oxidative stress response on microarray analysis and their autophagic activity is lowered through the mammalian target of rapamycin (mTOR)—unc-51-like kinase 1 pathway. Rapamycin attenuated podocyte dysfunction and extends survival in Tsc2∆podocyte mice. Additionally, mTOR complex 1 (mTORC1) activity is increased in podocytes of renal biopsy specimens obtained from obese patients with chronic kidney disease. Our work shows that mTORC1 hyperactivation in podocytes leads to severe renal dysfunction and that inhibition of mTORC1 activity in podocytes could be a key therapeutic target for obesity-related kidney diseases.

2020-03-21 | GSE106828 | GEO

Human iPSC derived glomeruli facilitate accurate modelling of podocytopathy

Project description:Podocytes are the highly specialised cells within the glomeruli of the kidney that maintain the filtration barrier by forming interdigitating foot processes and slit-diaphragms. Disruption to these features result in proteinuria. Studies into podocyte biology and disease has been hampered by a paucity of in vitro models of this non-proliferative cell type. Here we characterise sieved glomeruli from kidney organoids derived from human pluripotent stem cells. Compared to conditionally immortalised podocytes, organoid-derived glomeruli show superior podocyte-specific gene and protein expression, morphology and functional properties. Using CRISPR-derived MAFB reporter iPSC lines, homozygous MAFB mutant organoids recapitulated the anticipated disease related transcriptional changes. Culture of kidney organoids on chicken chorioallantoic membrane resulted in glomerular vascularisation, glomerular filtration barrier assembly, formation of slit diaphragms and fenestrated endothelial cells. This definitively demonstrates that human iPSC kidney organoid-derived glomeruli can serve as an accurate model of human podocytopathies and glomerular disease in vitro.

2018-12-04 | GSE99583 | GEO

Exon Level Expression Profiling of Diabetic Nephropathy

Project description:Transcriptome comparison of glomeruli from kidneys with diabetic nephropathy (DN) and glomeruli from the unaffected portion of tumor nephrectomies. Transcritomics profile of glomeruli in DN patients explored SRGAP2 was strongly associated with proteinuria and involved in podocyte cytoskeleton organization

2018-07-31 | GSE96804 | GEO

Comparison of Glomerular and Podocyte mRNA Profiles in eNOS-/- Diabetic Mice Induced by Streptozotocin

Project description:We compared mRNA profiles of isolated glomeruli versus sorted podocytes between diabetic and control mice. IRG mice crossed with eNOS-/- mice were further bred with podocin-rTTA and TetON-Cre mice to permanently label podocytes before the diabetic injury. Diabetes was induced by injection of streptozotocin. mRNA profiles of isolated glomeruli and sorted podocytes from diabetic and control mice at 10 weeks after induction of diabetes were examined. Consistent with the previous reports, expression of podocyte-specific markers in the glomeruli were down-regulated in the diabetic mice compared to controls. However, these differences disappeared when mRNA levels were corrected for podocyte number per glomerulus. Interestingly, the expression of these markers was not altered in sorted podocytes from diabetic mice, suggesting that the reduced expression of podocyte markers in isolated glomeruli is likely a secondary effect of reduced podocyte number, rather than the loss of differentiation markers. Analysis of the differentially expressed genes in diabetic mice also revealed distinct up-regulated pathways in the glomeruli (mitochondrial function and oxidative stress) and podocytes (actin organization). In conclusion, our data suggest that podocyte-specific gene expression in transcriptome obtained from the whole glomeruli may not represent those of podocytes in the diabetic kidney. We compared mRNA profiles of isolated glomeruli versus sorted podocytes between diabetic and control mice.

2016-03-16 | E-GEOD-79291 | biostudies-arrayexpress

Transcriptome profiling of renal glomeruli from Parva-fl/fl*hNPHS2Cre and WT mice

Project description:Podocyte specific knockout mice for Parva (Parva-fl/fl*hNPHS2Cre) were generated. Transcriptome profiling (RNA-Seq) and differential gene expression analysis of isolated renal glomeruli from KO and WT mice was performed. Parva KO mice showed transcriptional changes associated with podocyte and glomerular disease.

2022-01-20 | GSE181690 | GEO

Glomerular RNA-seq data of the kidney podocyte-specific Hdac1 and Hdac2 deficient mice

Project description:Podocyte histone deacetylases (HDAC) are essential in maintaining a normal glomerular filtration barrier by modulating podocyte quiescence. Podocyte-specific loss Hdac1 and 2 in mice results in severe proteinuria and sustained DNA damage, likely caused by epigenetic alterations and deficient DNA repair, that result in podocyte senescence. Through glomeruli isolation and RNA-seq profiling from the mutant mice, we demonstrated that senescent podocytes develop a senescence-associated secretory phenotype (SASP) that contribute to the loss of podocytes. The role of HDACs in senescence may provide important clues in our understanding of how podocytes are lost following injury.

2022-10-25 | GSE216088 | GEO

Gene expression profile at single cell level of podocyte-specific I-PpoI expressing mice kidney cortex

Project description:To investigate the alterations in cell populations in the kidney after podocyte DNA DSBs, we performed single-cell RNA sequencing (scRNA-seq) on the renal cortex of 12-week-old podocyte-specific I-PpoI expressing mice that had not yet developed glomerulosclerosis or fibrosis.

2022-12-26 | GSE220478 | GEO

RNAseq analysis of glomerular transcriptome of wild-type vs. Podocyte Cosmc knockout

Project description:Cosmc is an obligate chaperone for C1GalT1 T transferase necessary for generating mature mucin-type O-glycans. Animals lacking Cosmc in glomerular podocytes develop proteinuria, glomerulosclerosis and progressive renal failure. This study was designed to examine transcriptome differences in 1 month male animals with and without podocyte Cosmc, a time point when proteinuria is established but glomerular architecture is still relatively intact.

2019-03-04 | GSE126217 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data