Acidosis activates the Nrf2-pathway in renal proximal tubule-derived cells through a crosstalk with renal fibroblasts
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ABSTRACT:
PROVIDER: PRJNA904711 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22390521_1.fastq.gz | Fastqsanger.gz | |||
| SRR22390521_2.fastq.gz | Fastqsanger.gz | |||
| SRR22390522_1.fastq.gz | Fastqsanger.gz | |||
| SRR22390522_2.fastq.gz | Fastqsanger.gz | |||
| SRR22390523_1.fastq.gz | Fastqsanger.gz |
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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.
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Project description:We performed bulk RNA-seq on primary and immortalized human renal proximal tubule epithelial cells (RPTECs) subjected to siRNA mediated TNIK silencing.
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Project description:Cultured cell lines are widely used for research in the physiology, pathophysiology, toxicology and pharmacology of the renal proximal tubule. The lines that are most appropriate for a given use depend on the genes expressed. New tools for transcriptomic and proteomic profiling using RNA-sequencing (RNA-Seq) and mass spectrometry make it possible to catalog expressed genes in each cell line. This data set is the protoemic data of Rat NRK-52E cell line. We concludeno cell line fully matched the transcriptome of native proximal tubule cells. However, some of the lines tested are suitable for the study of particular metabolic and transport processes seen in the proximal tubule.
2020-10-15 | PXD021160 | Pride
Project description:Purpose:Cultured cell lines are widely used for research in the physiology, pathophysiology, toxicology and pharmacology of the renal proximal tubule. The lines that are most appropriate for a given use depend on the genes expressed.We have used modern RNA-sequencing techniques to identify the gene expression profile of 14 different cell lines plus primary cultures of mouse proximal tubule and compare them to transcriptomes of native kidney proximal tubules. Methods: 14 different proximal tubule cell lines were grown on permeable supports under conditions specific for the respective lines. RNA-Seq followed standard procedures. Results and conclusion: Transcripts expressed in cell lines showed variable match to transcripts selectively expressed in native proximal tubule. Opossum kidney (OK) cells displayed the highest percentage match (45%) with pig kidney cells (LLC-PK1) close behind (39%). Much lower percentage matches were seen for various human lines including HK-2 cells (26%) and lines from rodent kidneys (18-23%).An online resource (https://esbl.nhlbi.nih.gov/JBrowse/KCT/) has been created for interrogation of the data.No cell line closely matched the transcriptome of native proximal tubule cells. However, some of the lines tested are suitable for the study of particular metabolic and transport processes seen in the proximal tubule.
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Project description:The kidneys are essential for eliminating drugs and chemicals from the human body, with renal epithelial cells being particularly vulnerable to damage caused by xenobiotics and their metabolites. Predicting renal toxicity before clinical trials remains a pressing challenge, necessitating more predictive in vitro models. However, the abundance of commercially available renal proximal tubule epithelial cell (RPTEC) sources complicates the selection of the most predictive cell types. This study compared RPTEC sources, including primary cells (Lonza) and various RPTEC lines, such as ciPTECs (Cell4Pharma), TERT1/RPTECs (ATCC), and HEK293 (GenoMembrane), alongside HepG2 cells for specificity comparison. We tested these cells' responses to 12 drugs to evaluate their predictive capabilities. Cells were cultured in 96-well or 384-well plates and exposed to drugs for 72 hours at concentrations ranging from 0.3 to 300 µM. The CellTiterGlo® assay measured cell viability, and transcriptome data from unexposed cells analyzed gene expression profiles using the TempO-seq® S1500+ panel. Cell viability data determined points of departure (PODs), compared to human serum Cmax,free values to assess safety margins. Gene expression showed primary kidney cells closely matched the human kidney medulla, followed by TERT1 and ciPTEC lines, with HEK lines showing the least correlation. This study highlights differences among RPTEC sources and their utility in drug safety studies for the renal proximal tubule, emphasizing unique gene expression patterns related to metabolism, ion transport, and cell development, which are vital for improving predictive models in renal toxicity assessment.
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Project description:Aim of the study was to characterize the transcriptional response of human primary renal proximal tubule endothelial cells (RPTEC) to low oxygen stress. Experiment Overall Design: Passage 4 renal proximal tubule epithelial cells were exposed to a humidified atmosphere consisting of either 5% CO2 and 95% air (20% O2, normoxia) or 5% CO2, 1% oxygen and 95% nitrogen (hypoxia) for 24 hours. Total RNA was extracted immediately after exposure. Three independent biological replicates were performed, resulting in 6 samples (3 control and 3 low oxygen).
2008-10-25 | E-GEOD-12792 | biostudies-arrayexpress
Project description:Renal proximal tubule cell state and metabolism are coupled by nuclear receptors
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Project description:Lowe syndrome and Dent II disease are X-linked monogenetic diseases characterised by a renal reabsorption defect in the proximal tubules and caused by mutations in the OCRL gene, which codes for an inositol-5-phosphatase. The life expectancy of patients suffering from Lowe syndrome is largely reduced because of the development of chronic kidney disease and related complications. There is a need for physiological human in-vitro models for Lowe syndrome/Dent II disease to study underpinning disease mechanisms and to identify and characterise potential drugs and drug targets. Here we describe a proximal tubule organ on chip model combining 3D tubule architecture with fluid flow shear stress, which phenocopies hallmarks of Lowe syndrome/Dent II disease. We demonstrate the principal suitability of our in-vitro model for drug target validation. Furthermore, using this model we demonstrate that proximal tubule cells lacking OCRL expression upregulate markers typical for epithelial-mesenchymal transition (EMT) including the transcription factor SNAI2/Slug and show increased collagen expression and deposition, which potentially contributes to interstitial fibrosis and disease progression as observed in Lowe syndrome and Dent II disease.
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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.
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