Bioinformatics Analysis of miRNAs Germacrone Protection of Diabetic Nephropathy
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE216437 | GEO | 2022/10/27
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptome comparison of glomeruli from kidneys with diabetic nephropathy (DN) and glomeruli from the unaffected portion of tumor nephrectomies. Transcritomics profile of glomeruli in DN patients explored SRGAP2 was strongly associated with proteinuria and involved in podocyte cytoskeleton organization
2018-07-31 | GSE96804 | GEO
Project description:Validation of predicted gene expression of human mesangial cells after 24h Tacrolimus stimulus Objective: To evaluate tacrolimus as therapeutic option for diabetic nephropathy (DN) based on molecular profile and network-based molecular model comparisons. Materials and Methods: We generated molecular models representing pathophysiological mechanisms of DN and tacrolimus mechanism of action (MoA) based on literature derived data and transcriptomics datasets. Shared enriched molecular pathways were identified based on both model datasets. A newly generated transcriptomics dataset studying the effect of tacrolimus on mesangial cells in vitro was added to identify mechanisms in DN pathophysiology. We searched for features in interference between the DN molecular model and the tacrolimus MoA molecular model already holding annotation evidence as diagnostic or prognostic biomarker in the context of DN. Results: Thirty nine molecular features were shared between the DN molecular model, holding 252 molecular features and the tacrolimus MoA molecular model, holding 209 molecular features, with six additional molecular features affected by tacrolimus in mesangial cells. Significantly affected molecular pathways by both molecular model sets included cytokine-cytokine receptor interactions, adherens junctions, TGF-beta signaling, MAPK signaling, and calcium signaling. Molecular features involved in inflammation and immune response contributing to DN progression were significantly downregulated by tacrolimus (e.g. the tumor necrosis factor alpha (TNF), interleukin 4, or interleukin 10). On the other hand, pro-fibrotic stimuli being detrimental to renal function were induced by tacrolimus like the transforming growth factor beta 1 (TGFB1), endothelin 1 (EDN1), or type IV collagen alpha 1 (COL4A1). Conclusion: Patients with DN and elevated TNF levels might benefit from tacrolimus treatment regarding maintaining GFR and reducing inflammation. TGFB1 and EDN1 are proposed as monitoring markers to assess degree of renal damage. Next to this stratification approach, the use of drug combinations consisting of tacrolimus in addition to ACE inhibitors, angiotensin receptor blockers, TGFB1- or EDN1-receptor antagonists might warrant further studies. comparison of gene expression of human mesangial cells after 24h Tacrolimus vs. Ctrl; 4 independent experiments were conducted (4xTacrolimus 24h and 4x ctrl. 24h with Drug solvent (DMSO))
2016-08-01 | E-GEOD-84908 | biostudies-arrayexpress
Project description:Validation of predicted gene expression of human mesangial cells after 24h Tacrolimus stimulus Objective: To evaluate tacrolimus as therapeutic option for diabetic nephropathy (DN) based on molecular profile and network-based molecular model comparisons. Materials and Methods: We generated molecular models representing pathophysiological mechanisms of DN and tacrolimus mechanism of action (MoA) based on literature derived data and transcriptomics datasets. Shared enriched molecular pathways were identified based on both model datasets. A newly generated transcriptomics dataset studying the effect of tacrolimus on mesangial cells in vitro was added to identify mechanisms in DN pathophysiology. We searched for features in interference between the DN molecular model and the tacrolimus MoA molecular model already holding annotation evidence as diagnostic or prognostic biomarker in the context of DN. Results: Thirty nine molecular features were shared between the DN molecular model, holding 252 molecular features and the tacrolimus MoA molecular model, holding 209 molecular features, with six additional molecular features affected by tacrolimus in mesangial cells. Significantly affected molecular pathways by both molecular model sets included cytokine-cytokine receptor interactions, adherens junctions, TGF-beta signaling, MAPK signaling, and calcium signaling. Molecular features involved in inflammation and immune response contributing to DN progression were significantly downregulated by tacrolimus (e.g. the tumor necrosis factor alpha (TNF), interleukin 4, or interleukin 10). On the other hand, pro-fibrotic stimuli being detrimental to renal function were induced by tacrolimus like the transforming growth factor beta 1 (TGFB1), endothelin 1 (EDN1), or type IV collagen alpha 1 (COL4A1). Conclusion: Patients with DN and elevated TNF levels might benefit from tacrolimus treatment regarding maintaining GFR and reducing inflammation. TGFB1 and EDN1 are proposed as monitoring markers to assess degree of renal damage. Next to this stratification approach, the use of drug combinations consisting of tacrolimus in addition to ACE inhibitors, angiotensin receptor blockers, TGFB1- or EDN1-receptor antagonists might warrant further studies.
2016-08-01 | GSE84908 | GEO
Project description:Urinary proteome was analyzed and quantified by Tandem Mass Tag (TMT) labeling followed by bioinformatics analysis to study DN pathophysiology and to identify biomarkers of clinical outcome. We included type 2 diabetic normotensive non-obese males with and without incipient DN (microalbuminuria). Sample collection included blood and urine at baseline (control and DN-basal) and, in DN patients, after 3 months of losartan treatment (DN-treated). Urinary proteome analysis identified 166 differentially abundant proteins between controls and DN patients, 27 comparing DN-treated and DN-basal patients, and 182 between DN-treated patients and controls. Mathematical modeling analysis identified 80 key proteins involved in DN pathophysiology, 15 in losartan effect and 7 of these 95 are essential in both processes. VCAM-1 and neprilysin are the only ones that are differentially expressed in the urinary proteome. We observed an increase of VCAM-1 urine levels in DN-basal patients compared to diabetic controls and an increase of urinary neprilysin in DN-treated patients with persistent albuminuria, the latter confirmed by ELISA . Our results point to neprilysin and VCAM-1 as potential candidates in DN pathology and treatment.
2018-05-22 | PXD009303 | Pride
Project description:Diabetic nephropathy (DN) is a leading cause of ESRD worldwide, but its molecular pathogenesis is not well-defined and there are no specific treatments. In humans, there is a strong genetic component determining susceptibility to DN. However, specific genes controlling DN susceptibility in humans have not been identified. Here we describe a new mouse model, combining type 1 diabetes with activation of the renin angiotensin system (RAS), which develops robust kidney disease with features resembling human DN: heavy albuminuria, hypertension and glomerulosclerosis. Additionally, there is a powerful effect of genetic background regulating susceptibility to nephropathy. The 129 strain is susceptible to kidney disease, whereas the C57BL/6 strain is resistant. To examine the molecular basis of this differential susceptibility, we analyzed the glomerular transcriptome of young mice with albuminuria but without detectable alterations in glomerular structure. We find dramatic difference in regulation of immune and inflammatory pathways with up-regulation of pro-inflammatory pathways in the susceptible (129) strain and coordinate down-regulation in the resistant (C57BL/6) strain, compared to their respective baselines. Many of these pathways were also up-regulated in a rat model and in humans with DN. Our studies suggest that genes controlling inflammatory responses, triggered by hyperglycemia and hypertension, may be critical early determinants of susceptibility to DN. The analysis was carried out on 2 strains of mice (129/SvEv and C57BL/6), each involving 2 genotypes (wild-type and RenTg/Ins2Akita mutations). Four replicates were used for each strain-genotype (with the exception of 129/SvEv wild-type mice, which had 3 replicates).
2016-08-13 | E-GEOD-85569 | biostudies-arrayexpress
Project description:Background: Hyperglycemia-induced transcriptional alterations lead to aberrant synthesis of a large number of pathogenetic molecules leading to functional and structural damage to multiple end organs including the kidneys. Diabetic nephropathy (DN) remains a major cause of end stage renal disease. Multiple epigenetic mechanisms, including alteration of long non-coding RNAs (lncRNAs) may play a significant role mediating the cellular transcriptional activities. We have previously shown that lncRNA ANRIL may mediate diabetes associated molecular, functional and structural abnormalities in DN. Here we explored downstream mechanisms of ANRIL alteration in DN. Methods: We used renal cortical tissues from ANRIL knockout (KO) mice and wild type (WT) mice, with or without streptozotocin (STZ) induced diabetes for RNA sequencing. The differentially expressed genes were identified using edgeR and DESeq2 computational methods. KEGG and Reactome pathway analyses and network analyses using STRING and IPA were subsequently performed. Results: Diabetic animals showed hyperglycemia, reduced body weight gain, polyuria and increased urinary albumin. Both albuminuria and polyuria were corrected in the KO diabetic mice. RNA analyses showed Diabetes induced alterations of a large number of transcripts in the wild type (WT) animals. ANRIL knockout (KO) prevented a large number of such alterations. The altered transcripts include metabolic pathways, apoptosis, extracellular matrix protein synthesis and degradation, NFKB related pathways, AGE-RAGE interaction pathways etc. ANRIL KO prevented majority of these pathways. Conclusion: These findings suggest that as ANRIL regulates a large number of molecules of pathogenetic significance, it may potentially be a drug target for DN and other chronic diabetic complications.
2022-03-06 | GSE197699 | GEO
Project description:Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal disease. Emerging evidence suggests that complement activation is involved in the pathogenesis of DN. The aim of this study was to investigate the pathogenic role of C3a and C3a receptor (C3aR) in DN. The expression of C3aR was examined in the renal specimen of DN patients. Using a C3aR gene knockout mice (C3aR-/-), we evaluated kidney injury in diabetic mice. The mouse gene expression microarray was performed to further explore the pathogenic role of C3aR. Then the underlying mechanism was investigated in vitro with macrophage treated with C3a. Compared with normal controls, the renal expression of C3aR was significantly increased in DN patients. C3aR-/- diabetic mice developed less severe diabetic renal damage compared with WT diabetic mice, exhibiting significantly lower level of albuminuria and milder renal pathological injury. Microarray profiling uncovered significantly suppressed inflammatory responses and T cell adaptive immunity in C3aR-/- diabetic mice compared with WT diabetic mice and this result was further verified by immunohistochemical staining of renal CD4+, CD8+ T cells and macrophages infiltration. In vitro study demonstrated C3a can enhance macrophages secreted cytokines which could induce inflammatory responses and differentiation of T cell lineage. In conclusion, C3aR deficiency could attenuate diabetic renal damage through suppressing inflammatory responses and T cell adaptive immunity, possibly by influencing macrophages secreted cytokines. Thus, C3aR may be a promising therapeutic target for DN.
2020-04-10 | GSE133597 | GEO
Project description:Diabetic nephropathy (DN) is a leading cause of end-stage kidney disease worldwide. Susceptibility to DN is inherited but genetic determinants of DN have not been precisely defined. We have previously described a mouse model combining genetic type 1 diabetes (Akita) with a renin transgene (ReninTg) that exhibits characteristic features of human DN including albuminuria, glomerulosclerosis, and genetic predisposition for kidney disease. We performed single-cell sequencing (10x Chromium) of glomerular cell suspensions obtained from the wildtype (WT) and Akita- ReninTg (AR) mice at 10 weeks of age before overt pathological abnormalities are present in kdiney.
2023-09-25 | GSE243995 | GEO
Project description:Diabetic nephropathy (DN) is a leading cause of ESRD worldwide, but its molecular pathogenesis is not well-defined and there are no specific treatments. In humans, there is a strong genetic component determining susceptibility to DN. However, specific genes controlling DN susceptibility in humans have not been identified. Here we describe a new mouse model, combining type 1 diabetes with activation of the renin angiotensin system (RAS), which develops robust kidney disease with features resembling human DN: heavy albuminuria, hypertension and glomerulosclerosis. Additionally, there is a powerful effect of genetic background regulating susceptibility to nephropathy. The 129 strain is susceptible to kidney disease, whereas the C57BL/6 strain is resistant. To examine the molecular basis of this differential susceptibility, we analyzed the glomerular transcriptome of young mice with albuminuria but without detectable alterations in glomerular structure . We find dramatic difference in regulation of immune and inflammatory pathways with up-regulation of pro-inflammatory pathways in the susceptible (129) strain and coordinate down-regulation in the resistant (C57BL/6) strain, compared to their respective baselines. Many of these pathways were also up-regulated in a rat model and in humans with DN. Our studies suggest that genes controlling inflammatory responses, triggered by hyperglycemia and hypertension, may be critical early determinants of susceptibility to DN.
2016-08-13 | GSE85569 | GEO
Project description:Gene expression profiling in glomeruli from human kidneys with diabetic nephropathy Keywords = Diabetes Keywords = kidney Keywords = glomeruli Keywords: other
2004-04-01 | GSE1009 | GEO