PAD4 deletion inhibited obstruction-induced kidney inflammation and fibrosis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE272378 | GEO | 2025/06/06
REPOSITORIES: GEO
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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:PAD4 deletion inhibited obstruction-induced kidney inflammation and fibrosis
| PRJNA1136535 | ENA
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
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:Interleukin (IL)-33 is a cytokine that appears to mediate fibrosis by signaling via its receptor ST2 (IL-33R/IL1RL1). It is also, however, a protein that after synthesis is sorted to the cell nucleus, where it appears to affect chromatin folding. Here we describe a novel role for nuclear IL-33 in regulating the fibroblast phenotype in murine kidney fibrosis driven by unilateral ureteral obstruction. Transcriptional profiling of IL-33-deficient kidneys 24h after ligation revealed enhanced expression of fibrogenic genes and enrichment of gene sets involved in extracellular matrix formation and remodeling. These changes relied on intracellular effects of IL-33, because they were not reproduced by treatment with a neutralizing antibody to IL-33 that prevents IL-33R/ST2L receptor signaling nor were they observed in IL33R/ST2-deficient kidneys. To further explore the intracellular function of IL-33, we established transcription profiles of human fibroblasts, observing that knockdown of IL-33 skewed the transcription profile from an inflammatory towards a myofibroblast phenotype, reflected in higher levels of COL3A1, COL5A1 and transgelin protein, as well as lower expression levels of IL6, CXCL8, CLL7 and CCL8. In conclusion, our findings suggest that nuclear IL-33 in fibroblasts dampens the initial profibrotic response until persistent stimuli, as enforced by UUO, can override this protective mechanism.
2020-05-06 | GSE149915 | 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: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: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: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
Project description:Lipid mal-metabolism, particularly fatty acid oxidation (FAO) dysfunction, is a major driver of renal fibrosis. However, detailed regulatory mechanisms underlying this process remain unclear. In this study, we demonstrated that acyl-CoA thioesterase 12 (Acot12) is a key regulator of lipid metabolism in fibrotic kidneys. A significantly decreased level of ACOT12 was observed in a kidney sample of human patients with chronic kidney disease as well as in mouse kidney injury. Acot12 deficiency induces lipid accumulation and fibrosis in mice subjected to unilateral ureteral obstruction (UUO). Fenofibrate administration does not reduce renal fibrosis in Acot12-/- mice with UUO. Moreover, restoration of peroxisome proliferator-activated receptor (PPAR in Acot12-/- Ppar-/- kidneys with UUO exacerbated lipid accumulation and renal fibrosis, whereas restoration of Acot12 in Acot12-/- Ppar-/- kidneys with UUO significantly reduced lipid accumulation and renal fibrosis suggesting, mechanistically, Acot12 deficiency exacerbates renal fibrosis independently of PPAR. In Acot12-/- kidneys with UUO, a reduction in the selective autophagic degradation of peroxisomes and pexophagy with a decreased level of ACBD5 was observed. In conclusion, our study demonstrates the functional role and mechanistic details of Acot12 in the progression of renal fibrosis, provides a preclinical rationale for regulating Acot12 expression and presents a novel means of preventing renal fibrosis.
2025-03-12 | GSE261115 | GEO