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Integrative omics analyses reveal epigenetic memory in diabetic cells regulating genes associated with kidney dysfunction. [microarray]

ABSTRACT: We report novel epigenetic mechanisms of epigenetic memory and its role in regulation of transporter genes in diabetic renal proximal tubules. We have generated RNA-seq, ATAC-seq and Infinium EPIC methylation array datasets from human primary proximal tubule epithelial cells from non-diabetic healthy controls and from patients with history of Type II Diabetes. Analyses of RNA-seq, ATAC-seq and Methylaiton EPIC array data.

ORGANISM(S): Homo sapiens

PROVIDER: GSE145745 | GEO | 2020/10/28

REPOSITORIES: GEO

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Integrative omics analyses reveal epigenetic memory in diabetic cells regulating genes associated with kidney dysfunction. [sequencing]

Project description:We report novel epigenetic mechanisms of epigenetic memory and its role in regulation of transporter genes in diabetic renal proximal tubules. We have generated RNA-seq, ATAC-seq and Infinium EPIC methylation array datasets from human primary proximal tubule epithelial cells from non-diabetic healthy controls and from patients with history of Type II Diabetes.

2020-10-28 | GSE145746 | GEO

Early Signaling Events in Renal Compensatory Hypertrophy Revealed by Multi-Omics

Project description:Loss of a kidney results in compensatory growth of the remaining kidney, a phenomenon of considerable clinical importance. However, the mechanisms involved are largely unknown. Here, we used a multi-omic approach in a mouse unilateral nephrectomy model to identify signaling processes associated with compensatory hypertrophy of the renal proximal tubule. Morphometry applied to microdissected proximal tubules showed that growth of the proximal tubule involves a marked, rapid increase in cell volume rather than cell number. Measurements of DNA accessibility (ATAC-seq), transcriptome (RNA-seq) and proteome (quantitative protein mass spectrometry) independently identified patterns of change that are indicative of activation of the lipid-regulated transcription factor, PPARα. Activation of PPARα by fenofibrate administration increased proximal tubule cell size, while genetic deletion of PPARα in mice decreased it. The results indicate that PPARα is an important determinant of proximal tubule cell size and is a likely mediator of compensatory proximal tubule hypertrophy.

2023-06-05 | PXD036395 | Pride

The changes of Chromatin Accessibiliy Triggered by Unilateral Nephrectomy [ATAC-seq]

Project description:Purpose: Experiments were done in mice undergoing unilateral nephrectomy (UNx) and sham nephrectomy. At specific time points (24 hours and 72 hours) after surgery, the earliest first portion of the kidney proximal tubule (PT-S1) and the cortical collecting duct (CCD) were manually micro-dissected and utilized for transcriptomic analysis by single-tubule small sample RNA-Seq and single-tubule ATAC seq. Methods: We carried out ATAC-sequencing in microdissected ealiest portion of proximal tubules (PT-S1) from mice with or without (sham) unilateral nephrectomy (UNx). Each group (Sham or UNx) has 3 biological replicates. Results and conclusion: ATAC-seq peaks in microdissected PT-S1 revealed a predominance of binding site motifs corresponding to PPARα.

2022-08-14 | GSE211022 | GEO

Circadian Gene Expression in Mouse Renal Proximal Tubule

Project description:Circadian variability in kidney function has long been recognized but is often ignored as a potential confounding variable in in vivo physiological experiments. To provide a guide for physiological studies on the kidney proximal tubule, we have now created a data resource consisting of expression levels for all measurable mRNA transcripts in microdissected proximal tubule segments from mice as a function of the time of day. This approach employs small-sample RNA-sequencing (RNA-seq) applied to microdissected renal proximal tubules including both S1 proximal convoluted tubules (PCTs) and S2 proximal straight tubules (PSTs). The data were analyzed using JTK-Cycle to detect periodicity. The data are provided as a user-friendly web page at https://esbl.nhlbi.nih.gov/Databases/Circadian-Prox/. In PCTs, 234 transcripts were found to vary in a circadian manner (3.7 % of total quantified). In PSTs, 334 transcripts were found to vary in a circadian manner (5.3 % of total quantified). Transcripts previously known to be associated with corticosteroid action and transcripts associated with increased flow were found to be overrepresented among circadian transcripts peaking during the “dark” portion of the day (Zeitgeber 14-22), corresponding to the peak levels of corticosterone and glomerular filtration rate in mice.

2023-04-10 | PXD039006 | Pride

Impact of Diabetic Stress Conditions on Renal Cell Metabolome

Project description:Diabetic kidney disease is a major complication in diabetes mellitus, and the most common reason for end-stage renal disease. Patients suffering from diabetes mellitus encounter glomerular damage by basement membrane thickening, and develop albuminuria. Subsequently, albuminuria can deteriorate the tubular function and impair the renal outcome. The impact of diabetic stress conditions on the metabolome was investigated by untargeted gas chromatography-mass spectrometry (GC-MS) analyses. The results were validated by qPCR analyses. In total, four cell lines were tested, representing the glomerulus, proximal nephron tubule, and collecting duct. Both murine and human cell lines were used. In podocytes, proximal tubular and collecting duct cells, high glucose concentrations led to global metabolic alterations in amino acid metabolism and the polyol pathway. Albumin overload led to the further activation of the latter pathway in human proximal tubular cells. In the proximal tubular cells, aldo-keto reductase was concordantly increased by glucose, and partially increased by albumin overload. Here, the combinatorial impact of two stressful agents in diabetes on the metabolome of kidney cells was investigated, revealing effects of glucose and albumin on polyol metabolism in human proximal tubular cells. This study shows the importance of including highly concentrated albumin in in vitro studies for mimicking diabetic kidney disease.

2019-10-08 | MTBLS1093 | MetaboLights

Transcription profiling of mouse Clcn5 knockout in proximal tubules of the kidney

Project description:Dent disease has multiple defects attributed to proximal tubule malfunction including low molecular weight proteinuria, aminoaciduria, phosphaturia and glycosuria. In order to understand the changes in kidney function of the Clc5 transporter gene knockout mouse model of Dent disease, we examined gene expression profiles from proximal tubules of mouse kidneys. Overall 720 genes are expressed differentially in the proximal tubules of the Dent Clcn5 knockout mouse model compared to those of control wild type mice. The fingerprint of these gene changes may help us to understand the phenotype of Dent disease. Experiment Overall Design: Renal proximal tubules were dissected from wild type and Clcn5 knockout mice. Mice were anesthetized with halothane, the abdominal aorta of each animal was accessed and the left kidney was perfused with an ice-cold salt. Proximal tubule dissection was performed in an ice-cold salt solution. After dissection of approximately 80-100 segments of 2 mm in length per kidney, the RNA for 3-4 mice was combined to have enough RNA per chip. Experiment Overall Design: 3 microarrays each of wild type and knockout mouse proximal tubule were processed

2008-06-11 | E-GEOD-10162 | biostudies-arrayexpress

Genome-wide mapping of Hnf4a binding sites in the newborn mouse kidneys

Project description:Hnf4a is specifically expressed in developing proximal tubule cells in the newborn mouse kidney. In order to identify direct target genes of Hnf4a in the developing proximal tubules, we performed ChIP-Seq of Hnf4a in the mouse kidneys at P0.

2020-11-12 | GSE144824 | GEO

Profiling of Transcripts in Rat Proximal Tubule

Project description:Freshly isolated rat kidney proximal tubules were subjected for transcript profiling. Three microarray experiments were done to obtain the kidney proxmial tubule transcriptome.

2009-01-26 | E-GEOD-13668 | biostudies-arrayexpress

Effect of deletion of von-Hippel-Lindau (VHL) in the proximal tubule in diabetic kidney disease

Project description:To establish the role of proximal tubular hypoxia in diabetic kidney disease, we use a mouse line with a specific deletion of von-Hippel-Lindau (VHL) in the proximal tubule and treat them with streptozotocin (STZ) to induce a type I diabetes mellitus. 10 weeks after induction of diabetes mellitus samples were collected.

2022-08-08 | GSE210401 | GEO

Tissue-specific metabolic reprogramming drives nutrient flux in diabetic complications

Project description:Diabetes is associated with altered metabolism, but how altered metabolism contributes to the development of complications such as diabetic kidney disease is unknown. We used a systems approach with transcriptomics and mass spectrometry (MS)-based metabolomics to determine alterations in carbohydrate and lipid metabolism in kidney cortex tissue from 24-week-old BKS db/db diabetic mice and db/+ controls. Glomerular-deprived kidney cortex (kidney proximal tubule) gene expression was profiled and compared with metabolite data. Transcriptomic and metabolomic profiling demonstrated an increase in both glycolysis and fatty acid beta-oxidation,

2016-12-08 | GSE86300 | GEO

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