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Cortical kidney bulk RNA Sequencing in the reversible unilateral ureter obstruction model.

ABSTRACT: The kidney has limited capacity to regenerate following injury and preferentially repairs chronic injury with secreted extracellular matrix proteins. This can be a progressive process with functioning kidney tissue being replaced detrimentally with fibrotic scar tissue, ultimately leading to kidney failure. Using the reversible unilateral ureteric obstruction model, a model of reversable injury, we describe the transcriptomic changes that occur during obstructive renal injury and subsequent repair.

ORGANISM(S): Mus musculus

PROVIDER: GSE145053 | GEO | 2020/09/27

REPOSITORIES: GEO

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Single Cell Transcriptomics reveals renal myeloid dynamics post reversable unilateral ureteric injury

Project description:The kidney has limited capacity to regenerate following injury and preferentially repairs chronic injury with secreted extracellular matrix proteins. This can be a progressive process with functioning kidney tissue being replaced detrimentally with fibrotic scar tissue, ultimately leading to kidney failure. Whilst the renal response to injury has been well described it has been examined at whole organ resolution and there has been very limited description of the contribution of individual cells to the kidney’s reparative ability. Using the reversible unilateral ureteric obstruction model, a model of reversable injury, we describe the transcriptomic changes that occur during obstructive renal injury and subsequent repair at a single cell resolution and describe the altered myeloid cell populations and kinetics likely involved in ongoing tissue repair.

2020-09-27 | GSE140023 | GEO

Kidney proteomics in the unilateral ureter obstruction (UUO) mouse model

Project description:Treatments for kidney fibrosis represent an urgent yet unmet clinical need. Effective therapies are limited due to not well understood molecular pathogenesis. We aimed at generating a comprehensive and integrated multi-omics data set (RNA/ microRNA transcriptomics and proteomics) of fibrotic kidneys which will be searchable through a user-friendly web application. Therefore, two commonly used mouse models were utilized: a reversible chemical-induced injury model (folic acid (FA) induced nephropathy) and an irreversible surgical-induced fibrosis model (unilateral ureteral obstruction (UUO)). RNA and small RNA sequencing as well as MS/MS with 10-plex tandem mass tags proteomics were performed with kidney samples from different time points over the course of fibrosis development. In summary, we present temporal and integrated multi-omics data from fibrotic mouse kidneys which are accessible through an interrogation tool to provide a searchable transcriptome and proteome for kidney fibrosis researcher.

2019-05-09 | PXD010861 | Pride

Cortical kidney bulk RNA Sequencing in the reversible unilateral ureter obstruction model.

Project description:Cortical kidney bulk RNA Sequencing in the reversible unilateral ureter obstruction model.

| PRJNA605812 | ENA

Single Cell Transcriptomics reveals renal myeloid dynamics post reversable unilateral ureteric injury

Project description:Single Cell Transcriptomics reveals renal myeloid dynamics post reversable unilateral ureteric injury

| PRJNA588051 | ENA

Multi Omics analysis of fibrotic kidneys in two mouse models (Unilateral ureter obstruction (UUO) model MS data set)

Project description:Kidney fibrosis represents an urgent unmet clinical need due to the lack of effective therapies and inadequate understanding of the molecular pathogenesis. We have generated a comprehensive and integrated multi-omics data set (proteomics, mRNA and small RNA transcriptomics) of fibrotic kidneys that is searchable through a user-friendly web application. Two commonly used mouse models were utilized: a reversible chemical-induced injury model (folic acid (FA) induced nephropathy) and an irreversible surgically-induced fibrosis model (unilateral ureteral obstruction (UUO)). mRNA and small RNA sequencing as well as 10-plex tandem mass tag (TMT) proteomics were performed with kidney samples from different time points over the course of fibrosis development. The bioinformatics workflow used to process, technically validate, and integrate the single data sets will be described. In summary, we present temporal and integrated multi-omics data from fibrotic mouse kidneys that are accessible through an interrogation tool to provide a searchable transcriptome and proteome for kidney fibrosis researchers.

2019-05-07 | GSE126182 | GEO

Assessment of unilateral ureter obstruction with multi-parametric MRI.

Project description:PurposeQuantitative multi-parametric MRI (mpMRI) methods may allow the assessment of renal injury and function in a sensitive and objective manner. This study aimed to evaluate an array of MRI methods that exploit endogenous contrasts including relaxation rates, pool size ratio (PSR) derived from quantitative magnetization transfer (qMT), chemical exchange saturation transfer (CEST), nuclear Overhauser enhancement (NOE), and apparent diffusion coefficient (ADC) for their sensitivity and specificity in detecting abnormal features associated with kidney disease in a murine model of unilateral ureter obstruction (UUO).MethodsMRI scans were performed in anesthetized C57BL/6N mice 1, 3, or 6 days after UUO at 7T. Paraffin tissue sections were stained with Masson trichrome following MRI.ResultsCompared to contralateral kidneys, the cortices of UUO kidneys showed decreases of relaxation rates R1 and R2 , PSR, NOE, and ADC. No significant changes in CEST effects were observed for the cortical region of UUO kidneys. The MRI parametric changes in renal cortex are related to tubular cell death, tubular atrophy, tubular dilation, urine retention, and interstitial fibrosis in the cortex of UUO kidneys.ConclusionMeasurements of multiple MRI parameters provide comprehensive information about the molecular and cellular changes produced by UUO. Magn Reson Med 79:2216-2227, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

| S-EPMC5870889 | biostudies-literature

Axl-inhibitor bemcentinib alleviates mitochondrial dysfunction in the unilateral ureter obstruction murine model.

Project description:Renal fibrosis is a progressive histological manifestation leading to chronic kidney disease (CKD) and associated with mitochondrial dysfunction. In previous work, we showed that Bemcentinib, an Axl receptor tyrosine kinase inhibitor, reduced fibrosis development. In this study, to investigate its effects on mitochondrial dysfunction in renal fibrosis, we analysed genome-wide transcriptomics data from a unilateral ureter obstruction (UUO) murine model in the presence or absence of bemcentinib (n = 6 per group) and SHAM-operated (n = 4) mice. Kidney ligation resulted in dysregulation of mitochondria-related pathways, with a significant reduction in the expression of oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), citric acid cycle (TCA), response to reactive oxygen species and amino acid metabolism-related genes. Bemcentinib treatment increased the expression of these genes. In contrast, AKT/PI3K signalling pathway genes were up-regulated upon UUO, but bemcentinib largely inhibited their expression. At the functional level, ligation reduced mitochondrial biomass, which was increased upon bemcentinib treatment. Serum metabolomics analysis also showed a normalizing amino acid profile in UUO, compared with SHAM-operated mice following bemcentinib treatment. Our data suggest that mitochondria and mitochondria-related pathways are dramatically affected by UUO surgery and treatment with Axl-inhibitor bemcentinib partially reverses these effects.

| S-EPMC8335678 | biostudies-literature

Axl targeting in experimental unilateral ureteral obstruction

Project description:We investigated if Axl receptor tyrosine kinase was up-regulated in unilateral ureteral obstruction (UUO) and if blocking of Axl by a small molecule called BGB324 (also called Bemcentinib) reduces fibrosis development in the ligated kidney as compared to treatment with its vehicle alone.

2019-03-01 | GSE123674 | GEO

Kidney single cell sequencing results from 10-day unilateral ureteral obstruction mice

Project description:Renal fibrosis is a common consequence of various progressive nephropathies, including obstructive nephropathy, and ultimately leads to kidney failure. Infiltration of inflammatory cells is a prominent feature of renal injury after draining blockages from the kidney, and correlates closely with the development of renal fibrosis. However, the underlying molecular mechanism behind the promotion of renal fibrosis by inflammatory cells remains unclear. Herein, we showed that unilateral ureteral obstruction (UUO) induced Gasdermin D (GSDMD) activation in neutrophils, abundant neutrophil extracellular traps (NETs) formation and macrophage-to-myofibroblast transition (MMT) characterized by α-smooth muscle actin (α-SMA) expression in macrophages. Gsdmd deletion significantly reduced infiltration of inflammatory cells in the kidneys and inhibited NETs formation, MMT and thereby renal fibrosis. Chimera studies confirmed that Gsdmd deletion in bone marrow-derived cells, instead of renal parenchymal cells, provided protection against renal fibrosis. Further, specific deletion of Gsdmd in neutrophils instead of macrophages protected the kidney from undergoing fibrosis after UUO. Single-cell RNA sequencing identified robust crosstalk between neutrophils and macrophages. In vitro, GSDMD-dependent NETs triggered p65 translocation to the nucleus, which boosted the production of inflammatory cytokines and α-SMA expression in macrophages by activating TGF-β1/Smad pathway. In addition, we demonstrated that caspase-11, that could cleave GSDMD, was required for NETs formation and renal fibrosis after UUO. Collectively, our findings demonstrate that caspase-11/GSDMD-dependent NETs promote renal fibrosis by facilitating inflammation and MMT, therefore highlighting the role and mechanisms of NETs in renal fibrosis.

2024-04-19 | GSE264184 | GEO

ST2+ T-regulatory Cells in Renal Inflammation and Fibrosis following Ischemic Kidney Injury

Project description:The role of IL-33 and its receptor ST2 in kidney injury is not well understood. This study demonstrates the importance of ST2 expression on the T-regulatory cells (Tregs) for the resolution of renal injury by suppressing inflammation and fibrosis. Treg-specific deletion of ST2, detrimentally impacted late outcomes of renal injury worsening the impairment of kidney function, inflammation, and fibrosis.

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