An integrative analysis of renal miRNA- and mRNA-expression signatures in progressive chronic kidney disease
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PROVIDER: PRJNA259677 | ENA |
REPOSITORIES: ENA
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Project description:MicroRNAs (miRNAs) significantly contribute to chronic kidney disease (CKD) progression via regulating mRNA expression and abundance. However, their association with clinical outcome remains poorly understood. We performed large scale miRNA and mRNA expression profiling on cryo-cut renal biopsy sections from n=43 subjects. miRNAs differentiating stable and progressive cases were determined, and putative target mRNAs showing inversely correlated expression profiles were identified and further characterized. We found a downregulation of 7 miRNAs in the progressive phenotype, and an upregulation of 29 target mRNAs which are involved in inflammatory response, cell-cell-interaction, apoptosis, and intracellular signaling. Particularly a diminished expression of miR-206 in progressive disease correlated significantly with the upregulation of the target mRNAs CCL19, CXCL1, IFNAR2, NCK2, PTK2B, PTPRC, RASGRP1, and TNFRSF25, all participating in inflammatory pathways. Progressive cases also showed a decreased expression of miR-532-3p, and an increased expression of target transcripts MAP3K14, TNFRSF10B/TRAIL-R2, TRADD, and TRAF2, all being involved in apoptosis pathways. miR-206, miR-532-3p and all 12 mRNA targets correlated with the degree of histological damage. The identified renal miRNA- and mRNA-profiles, and biological pathways may represent regulatory mechanisms, which are commonly present in various kinds of progressive chronic kidney disease.
2015-12-31 | GSE45980 | GEO
Project description:MicroRNAs (miRNAs) contribute to chronic kidney disease progression via negatively regulating mRNA abundance. However, their association with clinical outcome remains poorly understood. We performed large-scale miRNA and mRNA expression profiling on cryo-cut renal biopsy sections from a discovery (n=43) and a validation (n=29) cohort. In the discovery cohort (GEO Series accession number GSE45980), miRNAs differentiating stable and progressive cases were determined, and putative target mRNAs showing inversely correlated expression profiles were identified. We found a downregulation of 7 miRNAs in the progressive phenotype, and an upregulation of 29 target mRNAs that are involved in inflammatory response, cell-cell-interaction, apoptosis, and intracellular signaling. Reduced expression of miR-206 in progressive disease correlated with the upregulation of the target mRNAs CCL19, CXCL1, IFNAR2, NCK2, PTK2B, PTPRC, RASGRP1, and TNFRSF25, all participating in inflammatory pathways. Progressive cases also showed a lower expression of miR-532-3p and an increased expression of cognate target transcripts MAP3K14, TNFRSF10B/TRAIL-R2, TRADD, and TRAF2, all being involved in apoptosis pathways. In the independent validation cohort (this set of arrays), we confirmed the decreased expression of miR-206 and miR-532-3p, and the inverse correlation of these miRNAs with the expression of 9 of the 12 target genes. The levels of the identified miRNAs and the target mRNAs correlated to histological damage indices. These results suggest the involvement of specific miRNAs and mRNAs in biological pathways associated with the progression of chronic kidney disease.
2015-12-31 | GSE60860 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-12-31 | GSE60861 | GEO
Project description:Chronic kidney disease (CKD) is a disease characterized by normal or reduced proteinuria, glomerular filtration rate, progressive damage to glomeruli, tubules, and interstitium. In this study, we performed RNA-seq reveals ultrasound-guided renal parenchymal infusion of mesenchymal stem cells in SD rats animal model in chronic kidney disease. Our results indicate that differential genes in the normal group(n=3) VS CKD group(n=3) and normal group(n=3) VS MSCs treatment group(n=3).
2024-10-03 | GSE275449 | GEO
Project description:CONTEXT Slowly progressive chronic tubulo-interstitial damage jeopardizes long-term renal allograft survival. Both immune and non-immune mechanisms are thought to contribute, but the most promising targets for timely intervention have not been identified. OBJECTIVE In the current study we seek to determine the driving force behind progressive histological damage of renal allografts, without the interference of donor pathology, delayed graft function and acute graft rejection. DESIGN We used microarrays to examine whole genome expression profiles in renal allograft protocol biopsies, and analyzed the correlation between gene expression and the histological appearance over time. The gene expression profiles in these protocol biopsies were then compared with gene expression of biopsies with acute T-cell mediated rejection. PATIENTS Human renal allograft biopsies (N=120) were included: 96 rejection-free protocol biopsies and 24 biopsies with T-cell mediated acute rejection. RESULTS In this highly cross-validated study, we demonstrate the significant association of established, ongoing and future chronic histological damage with regulation of adaptive immune gene expression (T-cell and B-cell transcript sets) and innate immune response gene expression (dendritic cell, NK-cell, mast cell and granulocyte transcripts). We demonstrate the ability of gene expression analysis to perform as a quantitative marker for ongoing inflammation with a wide dynamic range: from subtle subhistological inflammation prior to development of chronic damage, over moderate subclinical inflammation associated with chronic histological damage, to marked inflammation of Banff-grade acute T-cell mediated rejection. CONCLUSION Progressive chronic histological damage after kidney transplantation is associated with significant regulation of both innate and adaptive immune responses, months before the histological lesions appear. This study therefore corroborates the hypothesis that quantitative inflammation below the diagnostic threshold of classic T-cell or antibody-mediated rejection is associated with early subclinical stages of progressive renal allograft damage. We used microarrays to examine whole genome expression profiles in renal allograft protocol biopsies, and analyzed the correlation between gene expression and the histological appearance over time. The gene expression profiles in these protocol biopsies were then compared with gene expression of biopsies with acute T-cell mediated rejection. Human renal allograft biopsies (N=120) were included: 96 rejection-free protocol biopsies and 24 biopsies with T-cell mediated acute rejection.
2011-12-10 | E-GEOD-25902 | biostudies-arrayexpress
Project description:Background: Short-chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, are produced by gut microbiota through fermentation of complex carbohydrates that cannot be digested by the human host. They affect gut health and can contribute at the distal level to the pathophysiology of several diseases, including renal pathologies. Methods: SCFA levels were measured in chronic kidney disease (CKD) patients (n = 54) at different stages of the disease and associations with renal function and inflammation parameters were examined. The impact of propionate and butyrate in pathways triggered in tubular cells under inflammatory conditions was analysed using genome-wide expression assays. Finally, a pre-clinical mouse model of folic acid-induced transition from acute kidney injury to CKD was used to analyse the preventive and therapeutic potential of these microbial metabolites in the development of CKD. Results: Faecal levels of propionate and butyrate in CKD patients gradually reduce as the disease progresses, and do so in close association with established clinical parameters for serum creatinine, blood urea nitrogen and the estimated glomerular filtration rate. Propionate and butyrate jointly downregulated the expression of 103 genes related to inflammatory processes and immune system activation triggered by TNF-α in tubular cells. In vivo, the administration of propionate and butyrate, either before or soon after injury, respectively prevented and slowed the progression of damage. This was indicated by a decrease in renal injury markers, the expression of pro-inflammatory and pro-fibrotic markers, and recovery of renal function over the long term. Conclusions: Propionate and butyrate levels are associated with a progressive loss of renal function in CKD patients. Early administration of these SCFAs prevents disease advancement in a pre-clinical model of acute renal damage, demonstrating their therapeutic potential independently of the gut microbiota.
2024-05-02 | GSE221506 | GEO
Project description:CONTEXT Slowly progressive chronic tubulo-interstitial damage jeopardizes long-term renal allograft survival. Both immune and non-immune mechanisms are thought to contribute, but the most promising targets for timely intervention have not been identified. OBJECTIVE In the current study we seek to determine the driving force behind progressive histological damage of renal allografts, without the interference of donor pathology, delayed graft function and acute graft rejection. DESIGN We used microarrays to examine whole genome expression profiles in renal allograft protocol biopsies, and analyzed the correlation between gene expression and the histological appearance over time. The gene expression profiles in these protocol biopsies were then compared with gene expression of biopsies with acute T-cell mediated rejection. PATIENTS Human renal allograft biopsies (N=120) were included: 96 rejection-free protocol biopsies and 24 biopsies with T-cell mediated acute rejection. RESULTS In this highly cross-validated study, we demonstrate the significant association of established, ongoing and future chronic histological damage with regulation of adaptive immune gene expression (T-cell and B-cell transcript sets) and innate immune response gene expression (dendritic cell, NK-cell, mast cell and granulocyte transcripts). We demonstrate the ability of gene expression analysis to perform as a quantitative marker for ongoing inflammation with a wide dynamic range: from subtle subhistological inflammation prior to development of chronic damage, over moderate subclinical inflammation associated with chronic histological damage, to marked inflammation of Banff-grade acute T-cell mediated rejection. CONCLUSION Progressive chronic histological damage after kidney transplantation is associated with significant regulation of both innate and adaptive immune responses, months before the histological lesions appear. This study therefore corroborates the hypothesis that quantitative inflammation below the diagnostic threshold of classic T-cell or antibody-mediated rejection is associated with early subclinical stages of progressive renal allograft damage.
2011-12-10 | GSE25902 | GEO
Project description:The number of heart failure (HF) patients is increasing. HF is frequently accompanied by kidney dysfunction and such organ failure is closely related. Recent investigations revealed that increased renal venous pressure, rather than decreased cardiac output, causes the deterioration of kidney function in HF patients; however, the underlying responsible mechanisms are unknown. We demonstrated that reduced blood flow speed in peritubular capillaries (PTCs) by renal congestion and upregulation of nuclear factor-κB (NF-κB) signaling synergistically exacerbate kidney injury. We generated a novel mouse model with unilateral renal congestion by coarctation of the inferior vena cava between renal veins. Intravital imaging highlighted the notable dilatation of PTCs and decreased renal blood flow speed in the congestive kidney. Renal damage after ischemia reperfusion injury was exacerbated in the congestive kidney and accumulation of polymorphonuclear leukocytes (PMNs) within PTCs was observed at the acute phase after injury. Pharmacological inhibition of NF-κB ameliorated renal congestion-mediated exacerbation of kidney injury. In vitro, adhesion of PMNs on the TNFα-stimulated endothelial cells was accelerated by perfusion of PMNs at a slower speed, which was cancelled by the inhibition of NF-κB signaling. Our study demonstrates the importance of slower blood flow accompanying activated NF-κB signaling in the congestive kidney in the exacerbation of renal injury. These mechanisms may explain how increased renal venous pressure in HF patients causes the deterioration of kidney dysfunction. Inhibition of NF-κB signaling may be a therapeutic candidate for the vicious cycle between heart and kidney failure with increased renal venous pressure.
2024-02-16 | GSE166838 | GEO
Project description:The gene expression signature of the human kidney interstitium is not fully understood. Transcript expression of laser microdissected cortical interstitium (excluding tubules, glomeruli and large vessels) in 9 human reference nephrectomies was compared to 6 human diabetic kidney biopsy specimens. This transcriptomic data revealed novel interstitial markers and enrichment of relevant pathways. Analysis of diabetic interstitium uncovered genes with unchanged as well as down-regulated expression when compared to reference samples. Laser microdissection (LMD) methodology enables collection of transcriptomic data associated with renal interstitium to aid in interpretation of pathophysiology and precision medicine studies.
2020-12-22 | GSE163603 | GEO
Project description:We obtained gene-expression profiles of microdissected renal-tubule cells from patients with proteinuric nephropathies. Based on the renal function during follow-up, the patients were divided in stable (n=14) and progressive (n=7) subjects (table 1). The cells of interest were laser-capture microdissected from frozen sections from archived kidney biopsy material. Initially all samples were processed as technical duplicates (2 x 21 arrays); due to a large number of signal-negative spots several arrays were excluded leaving 36 arrays for analysis. The samples P2, P6, P7, S10, S13 and S14 were analysed as individual arrays, all other samples were analysed after combination of duplicate arrays. Quality control: To test for reproducibility we calculated the intra-array variability of the duplicate arrays. Duplicate arrays were combined before statistical analysis where applicable. Patient and control characteristics can be found in the manuscript and on our website Frozen kidney biopsies were stained for alkaline phospatase, then the tubule cells were lasercapture microdissected using the PixCell II Laser Capture Microdissection System and CapSure; LCM Caps. Set of arrays that are part of repeated experiments Disease State: samples from patients with proteinuric nephropathy (stable or progressive) Biological Replicate Computed
2008-12-23 | E-GEOD-11513 | biostudies-arrayexpress