Microarray analysis revealed novel genes and pathways associated with neonatal unilateral ureteral obstruction
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Apor Veres-Székely
PROVIDER: E-MTAB-4984 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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:To find miRNAs that involve in renal epithelial transition and renal fibrosis, we performed unilateral ureteral obstruction of mice for 7 days. After that, we harvested kidneys, and performed microarray of miRNA. Contralateral kidneys without ureteral obstruction were used as controls. miRNAs were purified from kidneys with ureteral obstruction and contralateral kidneys without ureteral obstruction. Then microarray of miRNA was performed (n=4). miRNAs up-regulated in kidneys with ureteral obsctruction compared with contralateral kidneys were sorted. We performed unilateral ureteral obstruction of mice for 7 days, and harvested kidneys.
2012-12-05 | E-GEOD-42716 | biostudies-arrayexpress
Project description:To find miRNAs that involve in renal epithelial transition and renal fibrosis, we performed unilateral ureteral obstruction of mice for 7 days. After that, we harvested kidneys, and performed microarray of miRNA. Contralateral kidneys without ureteral obstruction were used as controls. miRNAs were purified from kidneys with ureteral obstruction and contralateral kidneys without ureteral obstruction. Then microarray of miRNA was performed (n=4). miRNAs up-regulated in kidneys with ureteral obsctruction compared with contralateral kidneys were sorted.
2012-12-05 | GSE42716 | GEO
Project description:Renal fibrosis is the final common pathway for chronic kidney disease. However, the detailed mechanisms and therapeutic strategies for renal fibrosis have not been established. MicroRNAs (miRNAs) are small, non coding RNAs that regulate various pathological conditions and diseases. Previous studies reported that miRNAs play a pivotal role in renal fibrosis. However, the role of miRNAs in renal fibrosis has not been completely elucidated. Therefore, in this study, miRNAs on renal fibrosis was investigated in a renal fibrosis mouse model generated by unilateral ureteral obstruction. MiRNA microarray analysis revealed 109 miRNAs that were upregulated more than 2 fold and 113 miRNAs that were downregulated less than 0.5 fold in the kidney of UUO mice compared with control mice.
2021-01-07 | GSE162794 | GEO
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
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:Early stages of ureteral obstruction are marked by polyuria with impaired urinary concentrating ability, associated with loss of aquaporin-2 (AQP2) expression. Most mechanistic work in unilateral ureteral obstruction (UUO) models has been done at relatively late time points, making it difficult to discriminate the early effect on collecting ducts (CDs) in gene expression. Here, we use single-tubule RNA-Seq to identity signaling pathways at earlier time points after UUO in rat models.
2022-07-20 | GSE174289 | GEO
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
Project description:Axl targeting in experimental unilateral ureteral obstruction
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Project description:Collagen 17A1 (COL17A1) is induced in urothelium under disease conditions of urinary system organs, such as chronic nephritis and urinary obstruction. Thus, the ureters of Col17a1-knock out (KO) mice were injured by unilateral ureteral obsruction (UUO), and the gene expression was compared with those of wild-tyoe (WT).
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