Development of gene expression profiles in human chronic kidney disease
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE66494 | GEO | 2015/08/16
SECONDARY ACCESSION(S): PRJNA277139
REPOSITORIES: GEO
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Project description:A microarray analysis with renal biopsy specimens from CKD patients was conducted in order to identify the responsible genes associated with tubulointerstitial fibrosis and tubular cell injury in CKD. This study showed microarray profiles in total 53 biopsy specimens of CKD patients. In the discovery set, 554 down-regulated and 226 up-regulated signatures were identified. Then, the expressional changes of these genes were examined in the validation set. Gene expression profiles in human chronic kidney disease was explored using renal biopsy specimens. Two independent studies: discovery set and validation set were performed. This dataset is part of the TransQST collection.
2015-08-16 | E-GEOD-66494 | biostudies-arrayexpress
Project description:Kidney damage involves the progressive and inexorable destruction of tubular and glomerular system. However, it is known that the patients survive AKI often recover renal structure and function. Correspondingly, previous studies demonstrated tubular regeneration in mice after massive kidney injury and linked mouse Sox9+ renal progenitor cells to this process. Here we show that renal progenitor cells can be cloned from renal needle biopsy sample of CKD patients. Progenitor cells can readily assembly into “kidney organoids” expressing proximal/distal tubular cell markers in 3D culture.
2022-04-22 | GSE119426 | GEO
Project description:Males are 50% more likely to develop end stage kidney failure compared to women. In this study we wanted to find out the molecular mechanism responsible for this increased risk. We collected kidney samples from patients with and without kidney disease and performed a comprehensive gene expression analysis in healthy and diseased male and female kidneys. Interestingly, the set of gender biased genes in healthy kidneys were different from those in diseased kidneys indicating not only baseline gene expression differences but also that the male and female kidney respond differently to disease condition. Our studies indicate that men and women with kidney problems might need to be treated differently. Keywords: Gender difference We collected 42 kidney samples from healthy living transplant donors, nephrectomies and from diagnostic kidney biopsies. Preliminary studies did not show significant gene expression differences in control kidneys based on the collection method (i.e. living kidney biopsy vs. unaffected portion of tumor nephrectomy). We grouped the tissue samples based on the histological readings of the kidney biopsies. Samples with evidence of glomerular and tubulointerstitial fibrosis were assigned into the diseased group. Characteristics of the research participants indicate diverse ethnic and disease groups and mild (StageIII) CKD. The tissue was microdissected into glomerular and tubulointerstitial fractions and expression arrays were performed separately.
2010-04-13 | E-GEOD-12682 | biostudies-arrayexpress
Project description:Motivation and design: Renal tubulointerstitial injury is an important determinant of chronic kidney disease (CKD) progression, yet treatment is limited to renin angiotensin system blockade. Accordingly, we performed global expression profiling in a 2 × 2 factorial design (N = 8 in each group) on RNA extracted from male Col4a3–/– mice and littermate controls on a 129X1/SvJ background at 4 and 7 weeks of age. Col4a3–/– mice have a mutation in the gene encoding the α3 chain of type IV collagen, associated with proteinuria and progressive loss of kidney function. We analyzed expression with Affymetrix GeneChip Mouse Gene 2.0 ST Arrays and derived a novel CKD progression signature based on aging and disease in Col4a3–/– mice. Using our progression signature, we sought to repurpose existing drugs for the treatment of progressive CKD. Results: Computational drug repurposing with the Connectivity Map identified lysine deacetylase inhibitor, vorinostat, as a novel candidate treatment for this murine model of CKD. Treatment with vorinostat attenuated tubulointerstitial injury, fibrosis, and altered inflammation. Vorinostat administration significantly increased the lifespan of Col4a3–/– mice although effects on urinary albumin excretion, plasma creatinine, and blood urea nitrogen were modest. Conclusions: Our data suggest that expression profiling and computational drug repurposing can be used to identify novel drugs that may reverse gene expression changes in experimental CKD. Lysine deacetylase inhibition may be a novel treatment approach to CKD associated with proteinuria and progressive tubulointerstitial injury.
2020-01-31 | GSE137086 | GEO
Project description:Tubulointerstitial injury plays an important role in diabetic nephropathy (DN) progression; however, no reliable urinary molecule has been used to predict tubulointerstitial injury and renal outcome of DN clinically. In this study, based on tubulointerstitial transcriptome, we identified secretory leukocyte peptidase inhibitor (SLPI) as the molecule associated with renal fibrosis and prognosis of DN. In tubular cells, high glucose could upregulate SLPI, which bound with β-catenin and GSK-3β reciprocally, abolished the interaction between β-catenin and GSK-3β, diminished GSK-3β-regulated β-catenin phosphorylation and the subsequent ubiquitination and degradation, thus led to β-catenin signaling activation and renal fibrosis. Db/db mice injected with adenovirus carrying Slpi-3xflag-GFP (Ad-Slpi-GFP) developed β-catenin signaling activation in the proximal tubule, worse albuminuria and tubulointerstitial fibrosis. Conversely, Slpi knockout (KO) mice with STZ-induced DN developed less albuminuria, tubulointerstitial fibrosis and β-catenin signaling activation. Furthermore, clinical studies showed that urinary SLPI protein level (uSLPI/Cr) had significant correlation with intrarenal SLPI mRNA and interstitial fibrosis. In an independent prospective cohort enrolled 711 patients with biopsy proven DN, uSLPI/Cr level was significantly associated with eGFR slope and improved the prediction value of renal outcome. Together, our study identified SLPI as a novel critical regulator for the progression of tubulointerstitial injury, which may be used as an independent risk predictor of DN progression.
2022-08-03 | GSE158230 | GEO
Project description:Kidney transcriptome sequencing was applied to identify the top up-regulated genes in mice with AKI. The product of the top-ranked gene was identified in the tubular cells and urine both in mouse and human AKI. Data from two cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) ≥ 45ml/min/1.73m2 who survived for at least 90 days after AKI were used to derive and validate multivariable prediction models. AKI to CKD progression was defined as a persistent eGFR < 60ml/min/1.73m2 and with a minimum 25% reduction from baseline eGFR 90 days after AKI in patients with prehospitalization eGFR ≥ 60ml/min/1.73m2. AKI to advanced CKD was defined by a sustained reduction of eGFR < 30 ml/min/1.73m2 90 days after AKI in those with prehospitalization eGFR 45-60ml/min/1.73m2. Kidney cytokeratin 20 (CK20) was significantly up-regulated in injured proximal tubular cells and detectable in urine within 7 days after AKI. High concentrations of urinary CK20 (uCK20) were independently associated with the severity of histological AKI and the risk of AKI to CKD or advanced CKD progression. In Test set, the AUC of uCK20 for predicting AKI to CKD or advanced CKD was 0.80, outperformed currently used biomarkers for detecting kidney tubular injury. Addition of uCK20 to an established clinical model significantly improved the ability for predicting AKI-CKD progression with an AUC of 0.90, and largely improved the risk reclassification.In conclusion This finding highlighted uCK20 as a novel and useful predictor for AKI-CKD progression, and may provide a tool to early identify patients at high risk of CKD following AKI.
2024-08-01 | GSE266436 | GEO
Project description:TGF-β stimulates CCN2 expression which in turn amplifies TGF-β signaling. This process promotes extracellular matrix production and accelerates the pathological progression of fibrotic diseases. Alternative splicing plays an important role in multiple disease development, while U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an essential factor in the early steps of pre-mRNA splicing. However, the molecular mechanism underlying abnormal CCN2 expression upon TGF-β stimulation remains unclear. This study elucidates that SIRT4 acts as a master regulator for CCN2 expression in response to TGF-β by modulating U2AF2-mediated alternative splicing. Analyses of renal biopsy specimens from patients with CKD and mouse fibrotic kidney tissues revealed marked nuclear accumulation of SIRT4. The tubulointerstitial fibrosis was alleviated by global deletion or tubular epithelial cell (TEC)-specific knockout of Sirt4, and aggravated by adeno-associated virus-mediated SIRT4 overexpression in TECs. Furthermore, SIRT4 was found to translocate from the mitochondria to the cytoplasm through the BAX/BAK pore under TGF-β stimulation. In the cytoplasm, TGF-β activated the ERK pathway and induced the phosphorylation of SIRT4 at Ser36, which further promoted its interaction with importin α1 and subsequent nuclear translocation. In the nucleus, SIRT4 was found to deacetylate U2AF2 at K413, facilitating the splicing of CCN2 pre-mRNA to promote CCN2 protein expression. Importantly, exosomes containing anti-SIRT4 antibodies were found to effectively mitigate the UUO-induced kidney fibrosis in mice. Collectively, these findings indicated that SIRT4 plays a role in kidney fibrosis by regulating CCN2 expression via the pre-mRNA splicing.
2024-10-11 | GSE279225 | GEO
Project description:Chronic kidney disease (CKD) accelerates vascular calcification (VC) via phenotypic switching of vascular smooth muscle cells (VSMCs). We investigated the roles of circulating small extracellular vesicles (sEVs) between the kidneys and VSMCs and uncovered relevant sEV-propagated microRNAs (miRNAs) and their biological signaling pathways. We established CKD models in rats and mice by adenine-induced tubulointerstitial fibrosis. The miRNA transcriptome of sEVs revealed a depletion of several miRNAs in CKD. Their expression levels in sEVs from CKD patients were correlated to kidney function. This study revealed the transcriptomic landscape of miRNAs propagated in sEVs in CKD. We investigated the therapeutic potential of miRNAs in VC.
2022-12-31 | GSE217558 | GEO
Project description:Purpose: Transcriptiome profiling of chronic kidney disease Methods: Transcriptome profiling was performed in human renal biopsy tissue and correlated with parameters of kidney function, including estimated glomerular filtration rate (eGFR), degree of renal tubulointerstitial fibrosis (%TIF), as well as CKD progression over a median follow-up period of 60 months. Results: Transcriptome analysis performed in two independent cohorts of patients with CKD (n=24 and n=17, respectively) identified a cluster of genes (n=93) significantly correlated (FDR P<0.05) with eGFR and %TIF, and associated with CKD progression, with enrichment for pathways associated with inflammation and immune-cell mediated infiltration. Expression of FRMD3, a previously reported candidate gene from human genetics studies in CKD, was negatively correlated with indices of CKD severity and progression. Knockdown of FRMD3 in human kidney epithelial cells enhanced fibrotic responses to the cytokine transforming growth factor-beta (TGF-β1). Analysis of FRMD3 binding partners indicated enrichment of proteins implicated in mitochondrial function and remodeling of epithelial adherens junctions. Lentivirus-mediated knockdown of FRMD3 in renal tubule epithelial cells yielded a significant reduction (>35%) in NAD(P)H-dependent oxidoreductase activity, and a corresponding increase in caspase activity (50%). Conclusions: Using global transcriptome profiling we define a cluster of transcripts associated with severity of CKD and identify loss of FRMD3 expression as a potential molecular driver. Loss of FRMD3 expression may contribute to mitochondrial function and TIF.
2022-10-24 | GSE137570 | GEO
Project description:Chronic kidney disease (CKD) is characterized by a slow and gradual loss of kidney function, with glomerular filtration loss over months or years, inevitably leading to end-stage renal disease. The renal failure resulting from this irreversible process derives from fibrotic lesions of each compartment of the kidney; glomerulosclerosis, vascular sclerosis, and tubulointerstitial fibrosis. Here, we aimed to specify CKD-related injury markers through proteomics analysis in animal kidney tissues.
2021-01-19 | PXD016447 | Pride