Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CD47 modulates the interaction of γ-catenin with E-cadherin and participates in epithelial–mesenchymal transformation in lipid nephrotoxicity

ABSTRACT: Hyperlipidemia, an important risk factor for cardiovascular diseases and end-stage renal disease, often increases renal injury and compromises kidney function. In the present study, the kidney histology analysis in human samples showed that high lipid levels induced renal fibrosis. However, the mechanism of lipid nephrotoxicity remains unknown. We employed mice models of two kinds to further experiments. The kidney histology analysis in mouse showed that high lipid levels induced renal fibrosis that was further confirmed by Western blot and real-time PCR of fibrotic indexes (fibronection, collagenI and α-SMA). In Vitro analysis also supported that OX-LDL significantly induced fibrotic response in HK-2 tubular epithelial cells. To further ascertain the mechanism of high lipid-induced fibrosis, RNA-sequencing (RNA-Seq) was performed. Combined the Gene Ontology (GO) analysis results of differentially expressed mRNAs obtained by RNA-Seq with the results of LC-MS/MS and STRING Functional Association Networks showed that CD47 modulated the interaction of γ-catenin with E-cadherin and participated in epithelial–mesenchymal transformation in lipid nephrotoxicity. The inhibition of CD47 expression by transfected with shRNA plasmid or treated with anti-CD47 antibody in OX-LDL-treated tubular epithelial cells restored the expression of E-cadherin and attenuated renal injury including fibrosis and inflammatory response. These findings indicate that CD47 may be a therapeutic potential target for long-term lipid abuse-induced kidney injury.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161737 | GEO | 2021/03/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Protective Effects of Mitochondrial Fission Inhibition on Ox-LDL Induced VSMC Foaming via Metabolic Reprogramming

Project description:Atherosclerosis (AS) is one of the most common diseases in middle-age and elderly population. Lipid metabolism disorder induced foaming of vascular smooth muscle cell (VSMC) is an important pathological process of AS. Mitochondria plays an important role in lipids metabolism. While it is not known whether regulating mitochondrial function can protect ox-LDL induced VSMC foaming via metabolic reprogramming. With ox-LDL induced mouse model of VSMC injury, the injury effect of ox-LDL and the protective effect of mdivi-1, the mitochondrial fission inhibitor on mitochondrial morphology and function of VSMC, and the formation of lipid droplet were observed. With metabonomics and proteomics techniques, the main lipid metabolites and regulation proteins were identified. The results showed that Ox-LDL induced a significant mitochondrial fission and fragmentation of VSMC, and mitochondrial function disorder along with lipid deposition and foaming. Mdivi-1 significantly antagonized the damage effect of ox-LDL on mitochondrial morphology and function of VSMC, and blocked the lipid deposition. Metabonomics analysis found 848 different metabolites between ox-LDL and mdivi-1 treatment group, in which the lipid metabolites were the main, and heptadecanoic acid, palmitoleic acid and myristic acid were the critical metabolites changed most. Proteomics results showed that there were 125 differential expressed proteins between ox-LDL and mdivi-1 treatment, acetyl -CoA carboxylase1 and fatty acid synthase were the main differential expressed proteins. This study suggest that Mitochondrial fission plays an important role in VSMC lipid deposition and foaming. Inhibition of mitochondrial fission may effectively fight against ox-LDL induced lipid deposition and foaming of VSMC via improving mitochondrial function and metabolic reprogramming. This finding provides a new insight for prevention and treatment of AS.

2022-10-14 | PXD035671 | Pride

Expression data from ARPE-19 cells treated with LDL or ox-LDL

Project description:LDL or Ox-LDL 200ug/ml, which showed no loss of viability after a 48 hour exposure, induced a physiological and pathological transcriptional response, respectively. LDL induced a downregulation of genes associated with cholesterol biosynthesis while ox-LDL induced transcriptional alterations in genes related to inflammation, matrix expansion, lipid metabolism and processing, and apoptosis. Pentraxin-3 was secreted into the culture medium after RPE cells were stimulated with ox-LDL, and immunohistochemically evident in Bruchs membrane of human macular samples with age-related macular degeneration. ARPE-19 cells exposed to 200ug/ml ox-LDL had a 38% apoptosis rate compared to less than 1% when exposed to LDL or untreated controls (p<0.0001). While LDL induced a physiologic response by RPE cells, a pathological phenotypic response was seen after treatment with oxidatively modified LDL. The transcriptional, biochemical, and functional data provide initial support of a role for the hypothesis that modified LDLs are one trigger for initiating events that contribute to the development of age-related macular degeneration. Keywords: treatment with non-treatment control Human ARPE-19 cells were exposed to LDL or oxidatively modified LDL (ox-LDL) for 48 hours for RNA extraction and hybridization on Affymetrix microarrays. We sought to determine whether retina, pigment epithelial cells develop a pathologic phenotype after exposure to low density lipoproteins (LDL) that are oxidatively modified.We have made two comparsions: LDL treatment versus non-treatment; ox-LDL treatment versus non-treatment.

2006-09-01 | E-GEOD-5741 | biostudies-arrayexpress

Expression data from ARPE-19 cells treated with LDL or ox-LDL

Project description:LDL or Ox-LDL 200ug/ml, which showed no loss of viability after a 48 hour exposure, induced a physiological and pathological transcriptional response, respectively. LDL induced a downregulation of genes associated with cholesterol biosynthesis while ox-LDL induced transcriptional alterations in genes related to inflammation, matrix expansion, lipid metabolism and processing, and apoptosis. Pentraxin-3 was secreted into the culture medium after RPE cells were stimulated with ox-LDL, and immunohistochemically evident in Bruch’s membrane of human macular samples with age-related macular degeneration. ARPE-19 cells exposed to 200?g/ml ox-LDL had a 38% apoptosis rate compared to less than 1% when exposed to LDL or untreated controls (p<0.0001). While LDL induced a physiologic response by RPE cells, a pathological phenotypic response was seen after treatment with oxidatively modified LDL. The transcriptional, biochemical, and functional data provide initial support of a role for the hypothesis that modified LDLs are one trigger for initiating events that contribute to the development of age-related macular degeneration. Keywords: treatment with non-treatment control

2006-09-01 | GSE5741 | GEO

Chronic Kidney Disease in a Murine Model of non-Alcoholic Steatohepatitis (NASH)

Project description:Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) that underlies a growing prevalence of cirrhosis and liver cancer worldwide. Clinical studies suggest that NASH is an independent risk factor for chronic kidney disease (CKD), but models and mechanisms linking these two diseases are lacking. Here, we have characterized the renal function, histological features, and transcriptomic profile in a well-validated murine NASH model generated by feeding a western diet (WD), with high contents of fat, fructose, and cholesterol, combined with a low dose of weekly IP carbon tetrachloride (CCl4). NASH mice developed significant glomerulosclerosis, tubular epithelial cell injury, and interstitial fibrosis at an intermediate stage (12 weeks). Animals with advanced NASH (24 weeks) displayed renal dysfunction, proteinuria, and renal fibrosis characterized by increased collagen deposition as tubulointerstitial fibrosis, tubular atrophy, and inflammatory cell infiltration. Mice treated with a low dose of CCl4 alone did not develop renal injury, thereby excluding the possibility of CCl4-induced nephrotoxicity. Transcriptomic analysis of kidney cortices revealed differentially expressed genes (DEGs) that were highly enriched in mitochondrial dysfunction, ATP synthesis, and oxidative stress at the intermediate stage (12 weeks) and dysregulation of the immune response, lipid metabolic process, and insulin signaling pathways at the late stage (24 weeks). NRF-mediated oxidative stress pathway, Sirtuin signaling, and AMPK pathways were also highly enriched. Our results confirm a causative role of NASH in the development of CKD and reveal potential mechanisms of NASH-induced kidney injury. These findings establish valuable model to study the pathogenesis of NASH-associated CKD, an important feature of fatty liver disease that has been largely overlooked, yet has clinical and prognostic importance.

2021-09-19 | GSE184256 | GEO

A novel lncRNA XLOC_032768 rescues cisplatin-induced apoptosis of renal tubular cells and acute kidney injury by repressing TNF-α expression in trans-manner [mouse]

Project description:The cellular and molecular mechanisms by which cisplatin induces nephrotoxicity have been investigated extensively. However, the role of long non-coding RNAs (lncRNAs) in cisplatin-induced nephrotoxicity has not been received much attention. Here, we explore the functions and underlying mechanisms of a novel lncRNA XLOC_032768 in cisplatin-induced nephrotoxicity. Cisplatin treatment resulted in the apoptosis of renal epithelial cells in a mouse model and human renal proximal tubular epithelial cells (HK-2). By performing differentially expressed genes (DEGs) of the transcriptome data, we found the expression of lncRNA XLOC_032768 was significantly repressed by cisplatin treatment, which was also validated by RT-qPCR experiment of in vivo and in vitro model. Overexpression of lncRNA XLOC_032768 significantly inhibited the cisplatin-induced apoptosis of HK-2 and the expression of biomarkers for cisplatin-induced nephrotoxicity. Results from XLOC_032768 overexpression experiment revealed that XLOC_032768 target the tumor necrosis factor (TNF)-α in trans in HK-2 cells and mouse exposed to cisplatin. The administration of lncRNA XLOC_032768 attenuated renal dysfunction, morphological damage, and renal tubular cell injury, which was accompanied by TNF-α preservation, in a mouse model of cisplatin nephrotoxicity. These data indicate that XLOC_032768 suppressed cisplatin-induced apoptosis of tubular epithelial cells and acute kidney injury via a TNF mechanism. LncRNA XLOC_032768 would be a novel agent to reduce cisplatin-induced nephrotoxicity.

2021-07-27 | GSE142137 | GEO

A novel lncRNA XLOC_032768 rescues cisplatin-induced apoptosis of renal tubular cells and acute kidney injury by repressing TNF-α expression in trans-manner [human]

2021-07-27 | GSE142134 | GEO

Gene expression profiles in isolated proximal tubules and whole kidneys of rats after cisplatin-administration

Project description:To clarify the effects of cisplatin (cis-diamminedichloroplatinum II, CDDP) on the gene expression profiles in renal proximal tubules, microarray analyses were carried out using total RNA samples isolated from microdissected proximal tubules and whole kidneys. The molecular events underlying acute kidney injury (AKI) in the proximal tubules of rats with cisplatin-induced nephrotoxicity were successfully clarified with 17,000 transcripts. Renal proximal tubules were isolated under microscopy, and transcriptome data were collected with Rat Genome Survey MicroarrayÂ® (Applied Biosystems)

2013-12-24 | E-GEOD-37133 | biostudies-arrayexpress

RNAseq of kidneys from a mice model of chronic leptospirosis infection and induced a secondary nephrotoxic injury by adenine feeding

Project description:Background The mysterious chronic kidney disease is multifactorial causes. One of the risk factors is leptospirosis, a re-emerging infectious disease caused by Leptospira spp., for endemic leptospirosis tend to coincide with high-incidence regions of chronic kidney disease of unknown etiology. This study aims to investigate the role of leptospirosis as an emerging culprit in which chronic subclinical kidney injury, may predispose to progressive kidney disease when superimposed on secondary nephrotoxic injury. Methods Adenine-induced renal injury in chronic leptospira-infected C57/BL6 mice were studied for evaluating the renal function, histology and gene expression changes. We employed RNA sequencing-based renal transcriptome to investigate pathogenic pathways associated with secondary nephrotoxic injury in chronic kidney injury due to leptospirosis. Results The severity of kidney lesions was increased and the expression of immune/inflammation/fibrosis genes were significantly up-regulated in either low-dose (0.1%) and high-dose (0.2%) adenine-induced renal injury superimposed on infected mice. Whole renal transcriptome analysis reveals that the substantial amplification of the tremendous amount of expressed genes and fibrosis-related pathways was found in adenine-induced kidney injury add-on to leptospira-infected mice which correlated with kidney dysfunction and fibrosis compared to infection or adenine itself. A total of 41 differentially expressed genes associated with fibrosis were identified in infected mice fed with adenine, suggesting that these potential genes contributed to aggravated renal progression occurred in adenine-fed chronic leptospira-infected mice. Conclusions In summary, this study indicates that chronic subclinical kidney infection when exposed to different degree of secondary nephrotoxic injury may predispose to exacerbated and progressive chronic kidney disease.

2021-04-05 | GSE150641 | GEO

Proteomic analysis of cisplatin exposure on the kidney cortex proteome and the effect of preconditioning

Project description:Acute kidney injury and nephrotoxicity are important clinical side effects of cisplatin. Thus, the mechanisms of this disease, and potential treatment options are important to understand in their entity. Here, we analyzed the proteome of cisplatin induced acute kidney injury in a mouse model. Functionally we found that calorie restriction was able to completely blunt Cisplatin induced AKI, and hypoxia ameliorated cCisplatin induced AKI. To investigate the mechanism for this in high throughput, we performed label-free single-shot proteomic analyses of these kidneys.Acute kidney injury and nephrotoxicity are important clinical side effects of cisplatin. Thus, the mechanisms of this disease, and potential treatment options are important to understand in their entity. Here, we analyzed the proteome of cisplatin induced acute kidney injury in a mouse model. Functionally we found that calorie restriction was able to completely blunt Cisplatin induced AKI, and hypoxia ameliorated cCisplatin induced AKI. To investigate the mechanism for this in high throughput, we performed label-free single-shot proteomic analyses of these kidneys.

2020-01-30 | PXD005525 | Pride

Acyloxyacyl hydrolase protects against kidney injury via inhibition of tubular CD74-macrophage crosstalk

Project description:Renal fibrosis is the common pathway in the progression of chronic kidney disease (CKD). Acyloxyacyl hydrolase (AOAH) is expressed in various phagocytes and highly expressed in proximal tubular epithelial cells (PTECs). Research shows that AOAH plays a critical role in infections and chronic inflammatory diseases, although its role in kidney injury is unknown. Here, AOAH expression was examined in human and mouse kidneys, and Aoah-/- mice and single cell RNA sequencing (scRNA-seq) were performed to determine its role in kidney injury induced by folic acid (FA). We found that AOAH expression was positively correlated with estimated glomerular filtration rate (eGFR) while negatively correlated with the degree of renal fibrosis in kidneys of CKD patients. AOAH deletion led to exacerbated kidney injury and fibrosis after FA administration, which was reversed by overexpression of Aoah in kidneys. scRNA-seq revealed that Aoah-/- mice exhibited increased subpopulation of CD74+ PTECs, even though total PTECs were decreased compared to WT mice after FA treatment. Finally, exacerbated kidney injury and fibrosis seen in Aoah-/- mice was attenuated via administration of ISO-1, an inhibitor of macrophage inhibition factor (MIF) and CD74 binding. Thus, our work indicates that AOAH protects against kidney injury and fibrosis by inhibiting renal tubular epithelial cells CD74 signaling pathways. Targeting kidney AOAH represents a promising strategy to prevent renal fibrosis progression.

2023-12-01 | GSE234090 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data