Nfkb1 removal from proximal tubule cells improves renal tubular outcomes following ischemia reperfusion injury
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1252043 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33194336_1.fastq.gz | Fastqsanger.gz | |||
| SRR33194336_2.fastq.gz | Fastqsanger.gz | |||
| SRR33194337_1.fastq.gz | Fastqsanger.gz | |||
| SRR33194337_2.fastq.gz | Fastqsanger.gz | |||
| SRR33194338_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 28 |
Similar Datasets
Project description:CD73-derived adenosine plays an anti-inflammatory role in various organs. However, its role in renal ischemia-reperfusion injury (IRI) is controversial. We targeted CD73 mutant mice to determine the function of CD73 expressed by various renal cell types under mild IRI conditions. Mice with CD73 deletion in proximal tubules exhibited exacerbated IRI, comparable with that of CD73-/- mice compared with WT mice. Mice with CD73 deletions in other cell types, including cortical type 1 fibroblast-like cells, mesangial cells, macrophages, and dendritic cells, showed small or no increases in injury above control mice when subjected to threshold levels of ischemia. Results from adoptive transfer experiments between WT and CD73-/- mice and pharmacologic studies modulating enzymatic activity of CD73 and extracellular adenosine levels supported a critical role of adenosine generated by proximal tubule CD73 expression in abrogating IRI. Renal adenosine levels were lower before and after ischemia in CD73-deficient mice. However, reduction in total acid-extractable renal adenosine levels was inadequate to explain the marked difference in kidney injury in these CD73-deficient mice. Furthermore, CD73 inhibition and enzyme replacement studies showed no change in total kidney adenosine levels in treated mice compared with vehicle-treated controls. Protection from IRI in neutrophil-depleted WT recipients was sustained by repopulation with bone marrow neutrophils from WT mice but not by those lacking adenosine 2a receptors (from Adora2a-/- mice). These data support the thesis that local adenosine generated by cells at the injury site is critical for protection from IRI through bone marrow-derived adenosine 2a receptors.
| S-EPMC5328157 | biostudies-literature
Project description:Analysis of snATAC-seq data suggests increased motif of NFKB and AP-1 motifs of renal epithelia in kidney injury. To confirm binding sites we performed CUT&RUN of JUN and NFKB1 transcription factors in TNF-alpha treated cultured primary human renal proximal tubule cells.
2025-03-25 | GSE254187 | GEO
Project description:Studies in animal models have suggested a linkage between the inflammatory response to injury and subsequent nephron loss during the acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Failure of normal repair during the CKD transition correlates with de novo expression of vascular cell adhesion protein-1 (VCAM-1) by a subset of injured proximal tubule cells. This study identified the role of VCAM-1 expression in promoting the failed repair state. Single-cell transcriptome analysis of patients with AKI and CKD and whole kidney RNA and protein analyses of mouse models of CKD confirmed a marked increase of VCAM-1 expression in the proximal tubules of injured kidneys. In immortalized mouse proximal tubular cells and primary cultured renal cells (PCRCs), VCAM-1 expression was induced by proinflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Analyses of bulk RNA sequencing of TNF-α-treated primary cultured renal cells or pseudo-bulk RNA sequencing of biopsies from Kidney Precision Medicine Project datasets indicated activation of NF-κB and an enrichment of inflammatory response and cell adhesion pathways in VCAM-1-positive cells. Pharmacological inhibition of NF-κB signaling or genetic deletion of myeloid differentiation factor 88 and TIR domain-containing adapter-inducing interferon-β suppressed TNF-α- and IL-1β-induced VCAM-1 expression in vitro. TNF-α stimulation or overexpression of VCAM-1 significantly increased splenocyte adhesion to the mouse proximal tubular monolayer in culture. These results demonstrate that persistence of proinflammatory cytokines after AKI can induce NF-κB-dependent VCAM-1 expression by proximal tubule cells, mediating increased immune cell adhesion to the tubule and thus promoting further tubule injury and greater risk of progression from AKI to CKD.
2024-09-03 | GSE254359 | 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:Isolated proximal tubular cells from proximal tubular cell-specific KAT5 knockout mice for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain the physiological significance of KAT5 in proximal tubular cells.
2021-11-19 | GSE168535 | GEO
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
Project description:Proximal tubule has a remarkable capacity for repair after acute kidney injury. Whether dedifferentiation or a fixed progenitor population is responsible for this repair remains the subject of ongoing controversy. We have generated a novel genetic mouse model to address this question. We generated a Kim-1-GFPCreERt2 knockin mouse line (Kim1GCE) by homologous recombination. Kim-1 is expressed exclusively in dedifferentiated proximal tubule cells. We crossed this mouse line to the EGFP-L10a mouse line to perform Translating Ribosome Affinity Purification coupled with next generation sequencing (TRAP-seq) to identify the transcriptional signature of tubular epithelial cells during the course of injury and repair. TRAP-seq was performed in kidney samples at day 2, 7, and 14 after bilateral ischemia reperfusion injury and sham.
2019-11-29 | GSE121191 | GEO
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:We show the proximal tubular specific pathway analysis demonstrating the downregulation of oxidative phosphorylation in dapagliflozin treated db/db mice, a type 2 diabetic model. After 8-week treatment of dapagliflozin for db/db mice having proximal tubule specific tdTomato reporter, tdTomato-positive cells were isolated by FACS. Pathway analysis of RNA sequence of isolated tubular epithelia revealed that oxidative phosphorylation was downregulated in dapagliflozin-treated mice. However, depletion of renal tissue ATP content in db/db mice was ameliorated by dapagliflozin administration. Pimonidazole staining demonstrated that renal cortical tissue hypoxia was noted in db/db mice, which was improved by dapagliflozin administration. These findings suggest that dapagliflozin can ameliorated the excessive oxygen and ATP consumption and subsequent tissue hypoxia in diabetic kidney, which may explain, in part, the responsible mechanisms of renoprotecitive effect by dapagliflozin.
2022-09-28 | GSE185801 | GEO
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