DMM inhibited obstruction-induced renal fibrosis by blunting inflammation and activating PPAR signaling
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ABSTRACT:
PROVIDER: PRJNA1168603 | ENA |
REPOSITORIES: ENA
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Project description:To understand the roles and mechanisms of DMM in unilateral ureteral obstruction (UUO)-induced renal fibrosis, we performed RNA sequencing of UUO kidneys from mice treated with or without dimethyl malonate (DMM). DMM administration led to metabolic reprogramming in obstructed kidneys, the genes associated with the metabolism of fatty acid, organic acid, cellular amino acid, and mitochondrial function were significantly upregulated. Conversely, the downregulated genes in DMM-treated mice were involved in inflammation, including T cell immunity. Moreover, the upregulated genes in DMM-treated mice were associated with PPAR signaling. The RNA-seq analysis suggests that DMM activated PPAR and metabolic pathways while inhibited inflammatory signalings.
2025-07-02 | GSE278764 | GEO
Project description:PAD4 deletion inhibited obstruction-induced kidney inflammation and fibrosis
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Project description:To understand the roles and mechanisms of neutrophil extracellular traps (NETs) in unilateral ureteral obstruction (UUO)-induced renal fibrosis, we performed RNA sequencing of UUO kidneys from wild-type and PAD4-deficient mice. PAD4 deletion led to reduced expression of fibrosis- and injury-associated genes, as well as inflammatory cytokines in UUO kidneys. Enrichment analysis of the downregulated genes in PAD4-deficient mice revealed a drastic decrease in inflammation pathways, such as T cell-associated pathways and cytokine-cytokine receptor interaction.
2025-06-06 | GSE272378 | GEO
Project description:Methylobacter tundripaludum OWC-DMM genome sequencing
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Project description:Methylobacter tundripaludum OWC-DMM genome sequencing
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Project description:Objective: To Identify gene changes in the medial tibial plateau of articular cartilage at 2, 4 and 8 weeks after destabilisation of the medial meniscus (DMM) in mice and compare our data set with previously published sets to ascertain dysregulated pathways and genes in osteoarthritis. Materials and methods: RNA was extracted from the ipsilateral and contralateral medial tibial plateaus, amplified, labelled and hybridized on Illumina WG_v2 microarrays. Results were confirmed by RT-PCR for selected genes. Results: Transcriptional analysis and network reconstruction revealed changes in extracellular matrix (ECM) and cytoskeletal genes induced by DMM. TGFalpha signalling pathway and complement and coagulation cascade genes were regulated at 2 weeks. Fibronectin (FN1) is a hub in a reconstructed network of potential protein-protein interactions at 2 weeks. Regulated genes decrease over time and by eight weeks fibromodulin (FMOD) and tenascin N (TNN) are the only dysregulated genes present in the DMM operated knees. Comparison with human and rodent published gene sets discovered genes overlapping between our array and 6 others. Conclusions: Cartilage contributes a minute percentage to the RNA extracted from the whole joint (>0.2%), yet is sensitive to changes in gene expression post-DMM. The post-DMM transcriptional reprogramming wanes over time and dissipates by 8 weeks. Common pathways between published gene sets include focal adhesion, regulation of actin cytoskeleton and TGFalpha. Common genes include Jagged 1 (Jag1), Tetraspanin 2 (Tspan2), neuroblastoma, suppression of tumourigenicity 1 (Nbl1) and N-myc downstream regulated gene 2 (Ndrg2). The concomitant genes and pathways we identify are novel and warrant further investigation as biomarkers or modulators of osteoarthritis.
2014-01-08 | GSE53857 | GEO
Project description:Objective: To Identify gene changes in the medial tibial plateau of articular cartilage at 2, 4 and 8 weeks after destabilisation of the medial meniscus (DMM) in mice and compare our data set with previously published sets to ascertain dysregulated pathways and genes in osteoarthritis. Materials and methods: RNA was extracted from the ipsilateral and contralateral medial tibial plateaus, amplified, labelled and hybridized on Illumina WG_v2 microarrays. Results were confirmed by RT-PCR for selected genes. Results: Transcriptional analysis and network reconstruction revealed changes in extracellular matrix (ECM) and cytoskeletal genes induced by DMM. TGFalpha signalling pathway and complement and coagulation cascade genes were regulated at 2 weeks. Fibronectin (FN1) is a hub in a reconstructed network of potential protein-protein interactions at 2 weeks. Regulated genes decrease over time and by eight weeks fibromodulin (FMOD) and tenascin N (TNN) are the only dysregulated genes present in the DMM operated knees. Comparison with human and rodent published gene sets discovered genes overlapping between our array and 6 others. Conclusions: Cartilage contributes a minute percentage to the RNA extracted from the whole joint (>0.2%), yet is sensitive to changes in gene expression post-DMM. The post-DMM transcriptional reprogramming wanes over time and dissipates by 8 weeks. Common pathways between published gene sets include focal adhesion, regulation of actin cytoskeleton and TGFalpha. Common genes include Jagged 1 (Jag1), Tetraspanin 2 (Tspan2), neuroblastoma, suppression of tumourigenicity 1 (Nbl1) and N-myc downstream regulated gene 2 (Ndrg2). The concomitant genes and pathways we identify are novel and warrant further investigation as biomarkers or modulators of osteoarthritis. In total 18 samples. Each sample was a pool of the medial tibial plateau of 8 mice. Two categories (Treated and untreated) with three biological replicates each and three time points (2, 4 and 8 weeks post-surgery).
2014-01-08 | E-GEOD-53857 | biostudies-arrayexpress
Project description:Transcriptional profiling of mouse cartilage comparing destabilised medial meniscal operated knee joints to sham operated knee joints in both wild type C57Bl/6 and C57Bl/6 ADAMTS5Dcat mice at 1, 2 and 6 weeks post DMM surgery. The goal was to determine the differential gene expression with the onset of arthritis, both early, mid and late timepoints and to assess the gene expression differences when aggrecan loss is prevented in the ADAMTS5Dcat mouse. The overall design of the experiment is to compare DMM (right leg) to sham operated (left leg) cartilage from the same mouse. In order to identify genes involved in early and late arthritis, RNA was collected from cartilage samples from mice at 1, 2 and 6 weeks post surgery. In addition, to isolate genes differentially expressed downstream of aggrecan loss, the RNA as described was collected from C57Bl/6 wild type mice and ADAMTS5Dcat mice. Four mice were used at each timepoint with their left leg being the control Sham and their right leg the experimental DMM. One sample from the wild type 1wk post operation and one ADAMTS5Dcat dye swap were removed from the analysis for technical reasons.
2013-04-11 | E-GEOD-45793 | biostudies-arrayexpress
Project description:Urethra was partially ligated and the urinary bladder was removed 10 days or 6 weeks after obstruction. Sham operated rats were used as controls. An addtitonal group of rats were repoerated 6 weeks after surgery and the obstruction was removed. These rats were then sacrificed 10 days after deobstruction. The bladder (including the urothelium) was frozen and used for RNA extraction. Urinary bladders from sham-operated, 10 days and 6 weeks after obstruction and rats 10 days after deobstruction were compared. mRNA and microRNA were both analyzed.
2013-11-24 | E-GEOD-47080 | 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. We performed unilateral ureteral obstruction of mice for 7 days, and harvested kidneys.
2012-12-05 | E-GEOD-42716 | biostudies-arrayexpress