A comparison between novel 3D human renal proximal tubule organoids and 2D monolayer cells utilizing RPTEC-TERT1 cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE215254 | GEO | 2022/11/21
REPOSITORIES: GEO
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Project description:This study reports the cellular self-organization of primary human renal proximal tubule epithelial cells (RPTECs) around a minimal Matrigel scaffold to produce basal-in and apical-out proximal tubule organoids (tubuloids). These tubuloids are produced and maintained in hanging drop cultures for 90+ days, the longest such culture of any kind reported to date. The tubuloids upregulate maturity markers, such as aquaporin-1 (AQP1) and megalin (LRP2), and exhibit less mesenchymal and proliferation markers, such as vimentin and Ki67, compared to 2D cultures. They also experience changes over time as revealed by a comparison of gene expression patterns of cells in 2D culture and in day 31 and day 67 tubuloids. Gene expression analysis and immunohistochemistry reveal an increase in the expression of megalin, an endocytic receptor that can directly bind and uptake protein or potentially assist protein uptake. The tubuloids, including day 90 tubuloids, uptake fluorescent albumin and reveal punctate fluorescent patterns, suggesting functional endocytic uptake through these receptors. Furthermore, the tubuloids release kidney injury molecule-1 (KIM-1), a common biomarker for kidney injury, when exposed to albumin in both dose- and time-dependent manners. While this study focuses on potential applications for modeling proteinuric kidney disease, the tubuloids may have broad utility for studies where apical proximal tubule cell access is required.
2022-10-07 | GSE198857 | GEO
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
Project description:Global gene expression in the primary cultured mouse kidney proximal tubule cells treated either DMSO or 1uM GW4064 (a FXR agonist) was compared. Results provide insight into mechanisms underlying effects of FXR activation on gene expression in mouse kidney proximal tubule cells. Male C57/BJ mice aged 6 weeks were sacrificed under anesthesia and kidney proximal tubule cells were cultured until confluent. Cells were treated with either GW4064 (1uM) or equal amount of DMSO and incubated for 24 hours. 4 total RNA samples per group were analyzed and gene expression was compared between the groups.
2015-06-26 | E-GEOD-70296 | biostudies-arrayexpress
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
Project description:Injury to the proximal tubule plays a central role in the initiation and progression of kidney fibrosis, and rates of chronic kidney disease progresses approximately 50% faster in males compared to females. We applied Translating Ribosome Affinity Purification (TRAP) followed by RNA-sequencing to characterize the cell-specific proximal tubule transcriptional landscape during fibrosis in male vs. female mice.
2019-09-21 | GSE125015 | GEO
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:Global gene expression in primary cultured mouse kidney proximal tubule cells treated with either DMSO or 1uM GW4064 (an FXR agonist) was compared. Results provide insight into mechanisms underlying effects of FXR activation on gene expression in mouse kidney proximal tubule cells.
2015-06-26 | GSE70296 | GEO
Project description:The libraries contained in this experiment come from epithelial cells of proximal tubule (HRPTE piC). They are stranded PE101 Illumina Hi-Seq RAMPAGE libraries from rRNA-depleted Total RNA > 200 nucleotides in size. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2016-11-08 | GSE88603 | GEO
Project description:The proximal tubule plays an important role in the secretion and reabsorption of drugs in the kidney and is a major site of drug interaction and toxicity. Kidney toxicity analysis via in vitro assays is challenging as few provide appropriate proximal tubular cell function. In this study, we aimed to develop a simple and reproducible method to culture human proximal tubular epithelial cells (RPTECs), used in pharmacokinetic and toxicological evaluation by monitoring organic anion transporter (OAT)1 as a selection marker. As a result, by culturing RPTECs in spherical cellular aggregates, OAT1 protein expression, which does not increase in conventional 2D culture, increased over time and reached a similar level to that in human renal cortices from 5 different donors. The expression of proximal tubule markers, AQP1 and CDH6, was maintained, indicating that 3D RPTEC spheroids had proximal tubule characteristics. For SLC transporters, the 3D spheroid culture improved the protein expression of about 7% of the 139 transporter proteins detected and 2.3% of 4,800 proteins detected to about 5-fold that in human renal cortices. Furthermore, the protein expression levels of about 4800 proteins in 3D RPTEC spheroids (cultured for 12 days) were maintained over 20 days. Cisplatin and adefovir exhibited transporter-dependent ATP decreases in 3D RPTEC spheroids. These results indicate that the 3D RPTEC spheroid is a simple and robust in vitro experimental system for pharmacokinetic and toxicological evaluation in drug development.
2023-10-20 | GSE216153 | GEO
Project description:Systemic lupus erythematosus (SLE) is often considered a disease driven by autoreactive B cells and anti-nuclear antibodies. However, therapeutic targeting of B cells, for example through BAFF blockade, has been only partially effective in SLE. NF-κB Inducing Kinase (NIK) mediates non-canonical NF-κB signaling downstream of disease relevant TNF family members, such as BAFF, TWEAK, CD40, and OX40. We hypothesized that NIK inhibition might be more efficacious than BAFF blockade in lupus, and therefore generated highly selective and potent small molecule inhibitors (SMI) of NIK to test this hypothesis. RNASeq was used to investigate the effects of one of these SMIs of NIK, NIK SMI1, on TWEAK-stimulated Mouse renal proximal tubule-interstitial epithelial cells (RPTEC).
2017-10-26 | GSE89195 | GEO