RNAs sequencing revealing the gene expression profiling in kidney tissues between diabetic kidney disease and control
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE199838 | GEO | 2023/02/22
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE30528: Transcriptome Analysis of Human Diabetic Kidney Disease (DKD Glomeruli vs. Control Glomeruli) GSE30529: Transcriptome Analysis of Human Diabetic Kidney Disease (DKD Tubuli vs. Control Tubuli) GSE30566: Transcriptome Analysis of Human Diabetic Kidney Disease (Control Glomeruli vs. Control Tubuli) Refer to individual Series
2011-08-02 | E-GEOD-30122 | biostudies-arrayexpress
Project description:Analysis of gene expression changes in differentiated human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C). The hypothesis is that the three groups can be distinghed by their differential gene expression pattern. The results obtained revealed important information regarding differences in gene expression in human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C). Human podocytes were contacted with the serum from patients with diabetes and kidney disease (DKD+) or without kidney disease (DKD-) and compared to normal human podocytes contacted with serum from patients without diabetes (C).
2013-07-11 | E-GEOD-46897 | biostudies-arrayexpress
Project description:Analysis of gene expression changes in differentiated human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C). The hypothesis is that the three groups can be distinghed by their differential gene expression pattern. The results obtained revealed important information regarding differences in gene expression in human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C). Human podocytes were contacted with the serum from patients with diabetes and kidney disease (DKD+) or without kidney disease (DKD-) and compared to normal human podocytes contacted with serum from patients without diabetes (C).
2013-07-13 | E-GEOD-46899 | biostudies-arrayexpress
Project description:Analysis of gene expression changes in differentiated human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C). The hypothesis is that the three groups can be distinghed by their differential gene expression pattern. The results obtained revealed important information regarding differences in gene expression in human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C).
2013-07-11 | GSE46897 | GEO
Project description:Analysis of gene expression changes in differentiated human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C). The hypothesis is that the three groups can be distinghed by their differential gene expression pattern. The results obtained revealed important information regarding differences in gene expression in human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C).
2013-07-13 | GSE46899 | GEO
Project description:The pathogenesis of diabetic kidney disease (DKD) involves multifactorial processes that converge to initiate and advance the disease. Although DKD is not typically classified an inflammatory glomerular disease, mounting evidence supports the involvement of renal inflammation as a key contributor in DKD pathogenesis. However, detailed characteristics of specific immune cell types in the context of diabetic kidneys remain poorly understood. To capture the gene expression changes in specific immune cell subsets in early DKD, we performed a single-cell transcriptomic analysis of CD45-enriched kidney immune cells from control and diabetic OVE26 mice. Unsupervised clustering identified 11 distinct cell types that represented the major immune cells and an unidentified cell type. Further analysis of mononuclear phagocytes showed increased macrophage subsets in the diabetic kidneys and that pro-inflammatory and anti-inflammatory macrophages were concomitantly increased. Moreover, rather than in discrete M1 or M2 states, many macrophage subsets expressed genes consistent with the continuum of activation and differentiation states, and that their gene expression shifted toward increased inflammatory and differentiated status in the diabetic kidneys. Our study provides a comprehensive analysis of immune cell transcriptomic profiles in mouse DKD and underscores the dynamic macrophage activation in promoting DKD.
2022-11-08 | GSE195799 | GEO
Project description:Dyslipidemia is a significant risk factor for progression of diabetic kidney disease (DKD). To identify individual lipids and lipid networks that may be involved in DKD progression, we performed untargeted lipidomic analysis of kidney cortex tissue from diabetic db/db and db/db eNOS-/- mice along with nondiabetic littermate controls. A subset of mice were treated with the renin-angiotensin system (RAS) inhibitors, lisinopril and losartan, which improves the DKD phenotype in the db/db eNOS-/- mouse model. Of the three independent variables in this study, diabetes had the largest impact on overall lipid levels in the kidney cortex, while eNOS expression and RAS inhibition had smaller impacts on kidney lipid levels. Kidney lipid network architecture, particularly of networks involving glycerolipids such as triacylglycerols, was substantially disrupted by worsening kidney disease in the db/db eNOS-/- mice compared to the db/db mice, a feature that was reversed with RAS inhibition. This was associated with decreased expression of the stearoyl-CoA desaturases, Scd1 and Scd2, with RAS inhibition. In addition to the known salutary effect of RAS inhibition on DKD progression, our results suggest a previously unrecognized role for RAS inhibition on the kidney triacylglycerol lipid metabolic network. Keywords: Dyslipidemia is a significant risk factor for progression of diabetic kidney disease (DKD). To identify individual lipids and lipid networks that may be involved in DKD progression, we performed untargeted lipidomic analysis of kidney cortex tissue from diabetic db/db and db/db eNOS-/- mice along with non-diabetic littermate controls. A subset of mice were treated with the renin-angiotensin system (RAS) inhibitors, lisinopril and losartan, which improves the DKD phenotype in the db/db eNOS-/- mouse model. Of the three independent variables in this study, diabetes had the largest impact on overall lipid levels in the kidney cortex, while eNOS expression and RAS inhibition had smaller impacts on kidney lipid levels. Kidney lipid network architecture, particularly of networks involving glycerolipids such as triacylglycerols, was substantially disrupted by worsening kidney disease in the db/db eNOS-/- mice compared to the db/db mice, a feature that was reversed with RAS inhibition. This was associated with decreased expression of the stearoyl-CoA desaturases, Scd1 and Scd2, with RAS inhibition. In addition to the known salutary effect of RAS inhibition on DKD progression, our results suggest a previously unrecognized role for RAS inhibition on the kidney triacylglycerol lipid metabolic network.
2022-07-08 | GSE141680 | GEO
Project description:While blocking the renin angiotensin aldosterone system (RAAS) has been the main therapeutic strategy to control diabetic kidney disease (DKD) for many years, 25-30% of diabetic patients still develop the disease. In the present work we adopted a system biology strategy to analyze glomerular protein signatures to identify drugs with potential therapeutic properties in DKD acting through a RAAS-independent mechanism. Glomeruli were isolated from wild type and type 1 diabetic mice (Ins2Akita) treated or not with the angiotensin-converting enzyme inhibitor (ACEi) ramipril. Ramipril efficiently reduced the urinary albumin/creatine ratio (ACR) of Ins2Akita mice without modifying DKD-associated renal-injuries. Large scale quantitative proteomics was used to identify the DKD-associated glomerular proteins (DKD-GPs) that were ramipril-insensitive (RI-DKD-GPs). We then applied an in silico drug repurposing approach using a pattern-matching algorithm (Connectivity Mapping) to compare the RI-DKD-GPs’s signature with a collection of thousands of transcriptional signatures of bioactive compounds. The sesquiterpene lactone parthelonide was identified as one of the top compounds predicted to reverse the RI-DKD-GPs’s signature. Treatment of diabetic Ins2Akita mice with dimethylaminoparthenolide (DMAPT), a water soluble analogue of parthenolide, significantly reduced urinary ACR. However, in contrast to ramipril, DMAPT also significantly reduced glomerulosclerosis and tubulointerstitial fibrosis. Using a system biology approach we identified DMAPT, as a compound with a potential add-on value to standard-of-care ACEi-treatment in DKD.
2020-09-17 | PXD018728 | Pride
Project description:Background: Diabetes mellitus is the leading cause of cardiovascular and renal disease in the United States. In spite of all of the beneficial interventions implemented in patients with diabetes, there remains a need for additional therapeutic targets in diabetic kidney disease (DKD). Mitochondrial dysfunction and inflammation are increasingly recognized as important causes of the development and progression of DKD. However, the molecular connection between mitochondrial function, inflammation, and fibrosis remains to be elucidated. Methods: In the present studies we tested the hypothesis that enhancing NAD metabolism could increase mitochondrial sirtuin 3 (SIRT3) activity, improve mitochondrial function, decrease mitochondrial DNA damage, and prevent inflammation and progression of DKD. Results: We found that treatment of db-db mice with type 2 diabetes with nicotinamide riboside (NR) prevented albuminuria, increased urinary KIM1 excretion, and several parameters of DKD. These effects were associated with increased SIRT3 activity, improved mitochondrial function, and decreased inflammation at least in part via inhibiting the activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway. Conclusions: NR supplementation boosted the NAD metabolism to modulate mitochondrial function and inflammation and prevent progression of diabetic kidney disease.
2023-08-02 | PXD029745 | Pride
Project description:Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide. Therefore, efforts to understand DKD pathophysiology and prevent its development at the early phase are highly warranted. Here, we analyzed kidneys from healthy mice, diabetic mice, and diabetic mice treated with the sodium-glucose cotransporter 2 inhibitor dapagliflozin. Our combined method of ATAC and RNA sequencing revealed Csf2rb, Btla, and Isg15 as the key candidate genes associated with hyperglycemia, azotemia, and albuminuria. Their protein levels were altered together with multiple other inflammatory cytokines in the diabetic kidney, which was alleviated by dapagliflozin treatment. Cell culture of immortalized renal tubular cells and macrophages unraveled that dapagliflozin could directly effect on these cells in vitro as an anti-inflammatory agent independent of glucose concentrations. We further proved that dapagliflozin attenuated ischemia/reperfusion-induced chronic kidney injury and renal inflammation in mice. Overall, our data emphasize the importance of inflammatory factors to the pathogenesis of DKD, and provide valuable mechanistic insights into the renoprotective role of dapagliflozin.
2023-11-02 | GSE246763 | GEO