RNA sequencing of sham-operated and unilateral ureteral obstruction (UUO)-operated mouse kidneys in Pax8Cre+ and Kdm6afl/Y Pax8Cre+ knockout mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE205759 | GEO | 2023/09/01
REPOSITORIES: GEO
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Project description:Label-free quantitative proteomics for mouse kidney tissue of UUO vs Sham was used for discovery of differential expressed proteins in the process of renal fibrosis. Compared to sham mice, we found that 216 upregulated proteins and 215 downregulated proteins in UUO mice according to fold change ≥ 5, adjusted-p ≤ 0.01. Then, we will study the potential mechanism according to differential expressed proteins.
2022-09-30 | PXD029310 | Pride
Project description:INTRODUCTION AND OBJECTIVE: Loss of renal function is often the impetus for operative intervention in renal obstruction. Obstructive nephropathy is characterized discrete morphological and physiologic changes including tubular dilatation, apoptosis, and atrophy, as well as interstitial cellular infiltration and progressive interstitial fibrosis. We hypothesize that there are gene expression alterations correlated with obstructive nephropathy that could serve as biomarkers for early intervention. METHODS: C57BL/6 mice were subjected to Unilateral Urethral Obstruction (UUO) or sham surgery at postnatal day 21 of life, and kidneys were harvested after 1, 2, 5 and 9 days postoperatively. RNA was extracted from kidneys and comprehensive gene expression profiling was performed with Agilent microarrays. We used biological replicates: 13 UUO replicates, 9 sham replicates. 2-Channel microarrays were hybridized using universal reference in the Cy3 channel. Ingenuity pathway analysis was used to analyze the biological function and gene networks of gene expression data. RESULTS: Microarray analysis revealed more than 1800 transcripts that were up- or down-regulated over days 1 through 9 following obstruction, and included many transcripts reported previously (FOS, CD44, CLU, SPP1 and EGF). Pathway analysis revealed significant enrichment of transcripts in cell activation/differentiation, immune/inflammatory responses, cell cycle, metabolic process and transport. Interestingly, IPA network analysis showed that transcriptional regulatory pathway involving CEBPB/HNF4A is involved in obstructive nephropathy. CONCLUSIONS: Transcript profiling identified numerous gene expression changes following UUO and suggests a role for CEBPB/HNF4A pathway in obstructive nephropathy. This dataset provides a foundation for development of biomarkers for obstructive nephropathy. Time: day samples were collected post operation Somatic Modification: mice were operated on to generate urethral obstruction (Obstructed/Control) time_series_design
2012-11-01 | E-GEOD-36496 | biostudies-arrayexpress
Project description:INTRODUCTION AND OBJECTIVE: Loss of renal function is often the impetus for operative intervention in renal obstruction. Obstructive nephropathy is characterized discrete morphological and physiologic changes including tubular dilatation, apoptosis, and atrophy, as well as interstitial cellular infiltration and progressive interstitial fibrosis. We hypothesize that there are gene expression alterations correlated with obstructive nephropathy that could serve as biomarkers for early intervention. METHODS: C57BL/6 mice were subjected to Unilateral Urethral Obstruction (UUO) or sham surgery at postnatal day 21 of life, and kidneys were harvested after 1, 2, 5 and 9 days postoperatively. RNA was extracted from kidneys and comprehensive gene expression profiling was performed with Agilent microarrays. We used biological replicates: 13 UUO replicates, 9 sham replicates. 2-Channel microarrays were hybridized using universal reference in the Cy3 channel. Ingenuity pathway analysis was used to analyze the biological function and gene networks of gene expression data. RESULTS: Microarray analysis revealed more than 1800 transcripts that were up- or down-regulated over days 1 through 9 following obstruction, and included many transcripts reported previously (FOS, CD44, CLU, SPP1 and EGF). Pathway analysis revealed significant enrichment of transcripts in cell activation/differentiation, immune/inflammatory responses, cell cycle, metabolic process and transport. Interestingly, IPA network analysis showed that transcriptional regulatory pathway involving CEBPB/HNF4A is involved in obstructive nephropathy. CONCLUSIONS: Transcript profiling identified numerous gene expression changes following UUO and suggests a role for CEBPB/HNF4A pathway in obstructive nephropathy. This dataset provides a foundation for development of biomarkers for obstructive nephropathy. Time: day samples were collected post operation Somatic Modification: mice were operated on to generate urethral obstruction (Obstructed/Control)
2012-11-01 | GSE36496 | GEO
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
Project description:Significant renal fibrosis and a significant increase in serum creatinine were observed in AC model mice and UUO model mice, and the same pattern of fibrosis was observed in the cortex and medulla. Compared with sham operation, RNA-Seq detected circRNAs that were differentially expressed in the two models.
2022-03-01 | GSE192791 | GEO
Project description:Renal fibrosis (RF) is the common pathological outcome and central treatment target of multiple chronic kidney diseases. Currently, the molecular mechanisms of RF remain poorly understood. Therefore, this study aimed to established the adenine- and UUO-induced rat models, identified differentially expressed genes in their renal tissues using RNA-Seq analysis, and screened RF-related hub targets and key pathways.
2022-10-31 | GSE216376 | GEO
Project description:Congenital obstructive nephropathy (CON) is the leading cause of pediatric chronic kidney diseases with high morbidity and mortality.To identify differentially expressed genes, microarray analysis was performed using the unilateral ureteral obstruction (UUO)-induced neonatal rat model of CON.
2017-01-26 | E-MTAB-4984 | biostudies-arrayexpress
Project description:Chronic kidney disease (CKD) is a burden for Public Health and concerns millions of individuals worldwide. Independently of the cause, CKD is secondary to the replacement of functional renal tissue by extra-cellular matrix proteins (i.e fibrosis) that progressively impairs kidney function. The pathophysiological pathways that control the development of renal fibrosis are common to most of the nephropathies involving native kidneys or kidney grafts. Unfortunately, very few treatments are available to stop renal fibrosis and most of the therapeutic strategies are often barely able to slow down the progression of fibrogenesis in native kidneys. Therefore, it is mandatory to discover new therapeutic pathways to stop renal fibrosis. Our objective is to study new pathways involved in renal fibrosis. We thus decided to use the model of Unilateral Ureteral renal Obstruction in mice, a fast and reproducible experimental model of renal fibrosis. We studied renal fibrosis using experimental model of ureteral unilateral obstruction in mice, which was performed by complete ligation of the left ureter. The control lateral right kidney served as internal control.
2013-02-10 | E-GEOD-38117 | biostudies-arrayexpress
Project description:Profiling of miRNA expression in mouse SHAM kidneys 9–12 weeks old male C57BL/6 mice were purchased from Charles River. Mice underwent anesthesia by intraperitoneal injection of pentobarbital (50 mg/kg body weight) and were subjected to Unilateral Ureteral Obstruction (UUO). After standard laparotomy, the left proximal ureter was exposed and ligated with 4-0 silk at two points. The sham operation consisted of a similar identification of the left ureter without ligation. Treated (S numbers) and non-treated (C numbers) mice miRNA expressions were then compared.
2013-08-31 | E-GEOD-39831 | biostudies-arrayexpress
Project description:Obstructive nephropathy (ON) is a common clinical entity caused by different etiologies such as urolithiasis, prostatic hyperplasia in males, tumors, congenital stenosis, and others. Unilateral ureteral obstruction (UUO) in rodents is an experimental model widely used to explore the pathophysiology of ON, replicating vascular alterations, tubular atrophy, inflammation, and fibrosis development. On the other hand, mitochondria have been the subject of great attention, as morphological and functional alterations have been demonstrated in kidney diseases. Therefore, in this study, we explored the differences of the renal mitochondrial proteome during a time-course of 7, 14, and 21 days after the UUO in a rat model; and subsequently performed an overrepresentation analysis of biological processes to gain insight into the most relevant mitochondrial processes during UUO. We first isolated mitochondria from each UUO group and the control (sham) group, then the mitochondria were lysed in lysis buffer (8 M Urea, 20 mM HEPES, 1mM EDTA, pH 8.0) and digested using iST Sample Preparation Kit®. Peptides were separated using a UHPLC ACQUITY M-Class. Spectral data were acquired in an MS with electrospray ionization and ion mobility separation Synapt G2-Si operated with data-independent acquisition and ion mobility spectrometry in HDMSE mode. A total of 954 proteins were identified and quantified by label-free with Progenesis QI software and the database UP000002494 . Subsequently, after cross-checking with the MitoMiner database, we were left with 379 mitochondrial or mitochondrial transit proteins. Then, only proteins that had abundance values in at least 50% of the samples per study group and did not show atypical abundance values were selected, thus conserving 308 mitochondrial proteins for principal component analysis (PCA). PCA showed that 11 components can explain the total variation in protein abundance among samples and that the first two components can differentiate between the control group (sham) and the UUO groups. Considering the results obtained from the PCA analysis, a heat map was constructed with 243 proteins that strongly correlated (r ≤ -0.5 or r ≥ 0.5) with the first two principal components. The results show the abundance patterns for each UUO day and for the sham group and that these proteins are mainly involved in three metabolic pathways, oxidative phosphorylation (OXPHOS), the tricarboxylic acid cycle (TCA), and fatty acid (FA) metabolism.
2022-10-18 | PXD036205 | Pride