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RNA expression data from glomeruli lacking von Hippel-Lindau protein in podocytes

ABSTRACT: We and others have previously shown that glomerular endothelial cells and podocytes express hypoxia-inducible transcription factors (HIFs). HIFs bind to hypoxia response elements in target genes, such as vascular endothelial growth factor, which is continually produced by podocytes throughout life. To further assess function of HIFs in podocyte biology, podocin-Cre mice were mated with floxed von Hippel-Lindau (VHL) mice to selectively delete VHL, a component of an E3 ligase complex responsible for degradation of HIFs in normoxia. We reasoned that cells lacking VHL would overexpress stable HIFs and upregulate hypoxia-responsive genes. Progeny from these crosses displayed two phenotypes, non-proteinuric with glomerular basement membrane (GBM) defects and proteinuric with GBM defects and end-stage renal failure at ~6 months of age. Gene changes associated with the mild, non-proteinuric phenotype were studied using isolated glomeruli from wildtype and Pod-Cre fVHL mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE20235 | GEO | 2010/08/03

SECONDARY ACCESSION(S): PRJNA125735

REPOSITORIES: GEO

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RNA expression data from glomeruli lacking von Hippel-Lindau protein in podocytes

Project description:We and others have previously shown that glomerular endothelial cells and podocytes express hypoxia-inducible transcription factors (HIFs). HIFs bind to hypoxia response elements in target genes, such as vascular endothelial growth factor, which is continually produced by podocytes throughout life. To further assess function of HIFs in podocyte biology, podocin-Cre mice were mated with floxed von Hippel-Lindau (VHL) mice to selectively delete VHL, a component of an E3 ligase complex responsible for degradation of HIFs in normoxia. We reasoned that cells lacking VHL would overexpress stable HIFs and upregulate hypoxia-responsive genes. Progeny from these crosses displayed two phenotypes, non-proteinuric with glomerular basement membrane (GBM) defects and proteinuric with GBM defects and end-stage renal failure at ~6 months of age. Gene changes associated with the mild, non-proteinuric phenotype were studied using isolated glomeruli from wildtype and Pod-Cre fVHL mice. At 4 weeks of age, urine was collected and urinary albumin was quantified by Albuwell elisa from Pod-Cre fVHL litters. At 6 weeks of age, glomeruli from 3 wildtype littermate controls and 3 non-proteinuric Pod-Cre fVHL mice were collected using the magnetic bead method. RNA was extracted and hybridized to Affymetrix microarrays.

2010-08-03 | E-GEOD-20235 | biostudies-arrayexpress

MYDGF Deficiency Exacerbates Mitotic Catastrophe of Podocytes in Glomerular Disease

Project description:Podocytes, highly differentiated glomerular epithelial cells, are essential for the maintenance of glomerular filtration barrier. Podocyte dysfunction in podocytes is a major determinant of proteinuric kidney disease. By RNA sequencing analysis in ADR-treated podocytes with or without MYDGF overexpression, we observed the significant changes of genes important in regulating cell cycle in podocytes with ADR treatment.

2021-10-06 | GSE185226 | GEO

Elevation of JAML Promotes Diabetic Kidney Disease by Modulating Podocyte Lipid Metabolism

Project description:Podocytes, highly differentiated glomerular epithelial cells, are essential for the maintenance of glomerular filtration barrier. Lipid accumulation in podocytes is a major determinant of proteinuric kidney disease. By RNA-sequencing analysis, we observed the significant changes of genes important in regulating cellular lipid homeostasis in podocytes with HG treatment. We generated two mouse podocyte cell lines stably transduced with either a sh-NC lentiviral construct or a shRNA lentiviral construct designed to target JAML RNA to investigate the consequences on the gene expression profile of JAML knockdown in mouse podocytes.

2020-08-18 | GSE156367 | GEO

In silico nano-dissection: defining cell type specificity at transcriptional level in human disease (tubulointerstitium)

Project description:To identify genes with cell-lineage-specific expression not accessible by experimental micro-dissection, we developed a genome-scale iterative method, in-silico nano-dissection, which leverages high-throughput functional-genomics data from tissue homogenates using a machine-learning framework. This study applied nano-dissection to chronic kidney disease and identified transcripts specific to podocytes, key cells in the glomerular filter responsible for hereditary proteinuric syndromes and acquired CKD. In-silico prediction accuracy exceeded predictions derived from fluorescence-tagged-murine podocytes, identified genes recently implicated in hereditary glomerular disease and predicted genes significantly correlated with kidney function. The nano-dissection method is broadly applicable to define lineage specificity in many functional and disease contexts. We applied a machine-learning framework on high-throughput gene expression data from human kidney biopsy tissue homogenates and predict novel podocyte-specific genes. The prediction was validated by Human Protein Atlas at protein level. Prediction accuracy was compared with predictions derived from experimental approach using fluorescence-tagged-murine podocytes.

2013-08-06 | E-GEOD-47184 | biostudies-arrayexpress

In silico nano-dissection: defining cell type specificity at transcriptional level in human disease (glomeruli)

2013-08-06 | E-GEOD-47183 | biostudies-arrayexpress

Transcription profiling of mouse Podocytes reveal use of FcRn to clear IgG from the glomerular basement membrane

Project description:The glomerular filtration barrier prevents large serum proteins from being lost into the urine. It is not known, however, why the filter does not routinely clog with large proteins that enter the glomerular basement membrane (GBM). Here we provide evidence that an active transport mechanism exists to remove immunoglobulins that accumulate at the filtration barrier. We found that FcRn, an IgG and albumin transport receptor, is expressed in podocytes and functions to internalize IgG from the GBM. Mice lacking FcRn accumulated IgG in the GBM as they aged and tracer studies showed delayed clearance of IgG from the kidneys of FcRn deficient mice. Supporting a role for this pathway in disease, saturating the clearance mechanism potentiated the pathogenicity of nephrotoxic sera. These studies support the idea that podocytes play an active role in removing proteins from the GBM and suggest that genetic or acquired impairment of the clearance machinery is likely to be a common mechanism promoting glomerular diseases. Experiment Overall Design: Total RNA for genechip analysis was derived from two sources: Experiment Overall Design: 1) Primary mouse podocytes isolated by FACS sorting of collagenase digested glomeruli Experiment Overall Design: 2) In vitro differentiated conditionally immortalized mouse podocyte cell line. Experiment Overall Design: After obtaining genechip data, the expression of various IgG and albumin receptors was queried in the genechip data and then confirmed by RT-PCR.

2008-06-11 | E-GEOD-10017 | biostudies-arrayexpress

Gene expression analysis of a podocyte specific PTIP deletion in mouse glomerular preparations at 1 month of age

Project description:Glomerular RNA comparison between wild-type and podocyte specific deletion of the PTIP gene in 1 month old kidneys. The PTIP gene was deleted using a floxed allele and a Podocin-Cre driver strain. These mice develop protein urea by 3 months of age. This study was designed to find gene expression differences prior to the onset of the phenotype. A ptip floxed allele was crossed into the Podocin-Cre expressing strain to generate ptip fl/fl homozygous mice or ptip fl/- transheterozygous mice with or without the Cre expressing transgene. Animals were genotyped and assigend into two groups: Mutants with PTIP deletion (PTIP-) with the genotype ptip fl/fl:Pod-Cre or ptip fl/-:Pod-Cre or control mice (PTIP+) with either ptip fl/fl or ptip fl/-. Note that the floxed allele produced normal levels of wild-type PTIP protein. Kidneys were excised at 1 month of age. Glomeruli enriched fractions were generated by sieving of the tissue homogenates. RNA was prepared from glomerular enriched fractions.

2009-08-19 | E-GEOD-17709 | biostudies-arrayexpress

In silico nano-dissection: defining cell type specificity at transcriptional level in human disease (tubulointerstitium)

2013-08-06 | GSE47184 | GEO

In silico nano-dissection: defining cell type specificity at transcriptional level in human disease (glomeruli)

2013-08-06 | GSE47183 | GEO

Glomerular podocyte RNA-seq data of the podocyte-specific Profilin1 deficient mice

Project description:The progression of proteinuric kidney disease is associated with podocyte loss but the mechanisms remain unclear. Podocytes reenter the cell cycle to repair damaged ds DNA breaks. However, unsuccessful repair results in podocytes crossing the G1/S checkpoint and undergoes abortive cytokinesis. In this study, we identified Pfn1 as a major contributor in maintaining glomerular integrity and its loss in mice results in severe proteinuria, and kidney failure due to podocyte mitotic catastrophe, characterized by abundant multinucleated cells. Reentry of podocytes were identified by using FUCCI-2aR mice, accompanying the alteration of cell-cycle associated proteins, such as P21, P53, Cyclin B, and Cyclin D. Podocyte-specific translating ribosome affinity purification (TRAP) and RNAseq revealed a reduction of Ribosomal RNA-processing protein 8 (Rrp8) and re-expression of Rrp8 partially rescued the in-vitro phenotype. Clinical analysis of patients with proteinuric kidney disease demonstrated multinucleated podocytes and reduced podocyte profilin1 in kidney tissue. These results suggest that profilin is indispensible in regulating podocyte cell cycle and its disruption contributes to podocyte loss through mitotic catastrophe.

2023-12-01 | GSE227414 | GEO

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