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A 3D renal proximal tubule on chip model phenocopies Lowe syndrome and Dent II disease tubulopathy.

ABSTRACT: A 3D renal proximal tubule on chip model phenocopies Lowe syndrome and Dent II disease tubulopathy.

PROVIDER: PRJNA721193 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14208255_1.fastq.gz	Fastqsanger.gz
	SRR14208255_2.fastq.gz	Fastqsanger.gz
	SRR14208256_1.fastq.gz	Fastqsanger.gz
	SRR14208256_2.fastq.gz	Fastqsanger.gz
	SRR14208257_1.fastq.gz	Fastqsanger.gz

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A 3D renal proximal tubule on chip model phenocopies Lowe syndrome and Dent II disease tubulopathy.

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.

2021-05-21 | GSE171848 | GEO

3D vascularized proximal tubule model improves cell phenotype

Project description:3D vascularized proximal tubule model improves cell phenotype

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A comparison between novel 3D human renal proximal tubule organoids and 2D monolayer cells utilizing RPTEC-TERT1 cells

Project description:This experiment seeks to identify differences in human proximal tubule cells in 2D and 3D in response to nephrotoxins, identify early indications to predict toxicity

2022-11-21 | GSE215254 | GEO

Tnik depletion induces inflammation and apoptosis in injured renal proximal tubule epithelial cells

Project description:We performed bulk RNA-seq on primary and immortalized human renal proximal tubule epithelial cells (RPTECs) subjected to siRNA mediated TNIK silencing.

2024-04-10 | GSE216015 | 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

Proteomics of Rat Proximal-Tubule Cell-Culture Models

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

3D vascularized proximal tubule model improves cell phenotype

Project description:Cultured proximal tubule epithelial cells (PTECs) under physiological flow in a 3D channel embedded within an engineered extracellular matrix (ECM) that is colocalized with an adjacent channel lined with human glomerular endothelial cells (HGECs) to mimic a peritubular capillary. After a period of maturation under continuous flow, both cell types were harvested for RNAseq analyses. Our results revealed that PTECs’ transcriptional profile is highly dependent on both the matrix on which these cells are cultured and the flow conditions. By contrast, endothelial cells exhibit greater phenotypic plasticity and are affected by matrix, flow, and co-culture conditions.

2022-03-20 | GSE198822 | GEO

Transcriptomes of Major Proximal-Tubule Cell-Culture Models

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.

2020-10-14 | GSE135441 | GEO

Transcription profiling of human renal proximal tube endothelial cells at 24h and 1%oxygen

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

Renal proximal tubule cell state and metabolism are coupled by nuclear receptors

Project description:Renal proximal tubule cell state and metabolism are coupled by nuclear receptors

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