Dynaimic changes in glomerular cells in the development of diabetes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE219268 | GEO | 2023/10/27
REPOSITORIES: GEO
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Project description:Diabetic nephropathy is a chronic complication of diabetes, presenting albuminuria at an early stage and leading to renal failure. Kidney is a complicated organ, which is responsible for body fluids control, acid-base balance, and removal of toxins. To better understand the progress of diabetic nephropathy, mice renal cortex of control mice, six-week db-/- (increased serum glucose without pathological changes in kidneys), and ten-week db-/- (with pathological changes in kidneys) were collected for single-cell sequencing analyses. A subgroup of glomerular endothelial cells with pro-angiogenetic features was identified in diabetic kidneys.
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Project description:The objective of this study is to create an encyclopedia of all genes expressed in the glomerular endothelial cell under normal and diabetic conditions. We utilized Tie2-GFP transgenic mice to mark cells of the glomerular endothelium. To induce diabetic nephropathy (DB), a genetic model of DB, BKS.Cg-m +/+ Leprdb/J from Jax laboratories was used. We utilized fluorescent activated cell sorting (FACS) to isolate glomerular endothelial cells from normal and diabetic mice. The RNAs from these samples were isolated and utilized to hybridize to microarrays, which offers a powerful, efficient and effective method for the creation of a gene expression atlas. Microarrays were used to identify the transciptional differences that occur in the glomular endothelium of a diabetic mouse. Diabetic and control mice carrying the Tie2-GFP transgenic were utilized to isolate the endothelial cells from the adult glomerulus. The endothelial cells were isolated from the glomerulus using FACS. RNA was isolated and the gene expression profiles were determined by microarrays.
2010-08-16 | E-GEOD-21324 | biostudies-arrayexpress
Project description:The objective of this study is to create an encyclopedia of all genes expressed in the glomerular endothelial cell under normal and diabetic conditions. We utilized Tie2-GFP transgenic mice to mark cells of the glomerular endothelium. To induce diabetic nephropathy (DB), a genetic model of DB, BKS.Cg-m +/+ Leprdb/J from Jax laboratories was used. We utilized fluorescent activated cell sorting (FACS) to isolate glomerular endothelial cells from normal and diabetic mice. The RNAs from these samples were isolated and utilized to hybridize to microarrays, which offers a powerful, efficient and effective method for the creation of a gene expression atlas. Microarrays were used to identify the transciptional differences that occur in the glomular endothelium of a diabetic mouse.
2010-08-16 | GSE21324 | GEO
Project description:Diabetic nephropathy is a major cause of end-stage renal disease. Kidney podocytes play a central role in the pathogenesis of diabetic nephropathy. With their intercellular contacts they assemble part of the kidney filter. Many molecular mechanisms of the pathogenesis of diabetic nephropathy are not elucidated and targeted therapies are lacking. Nephron-specific TrkCknockout (TrkC-KO) and TrkC overexpressing mice exhibit features of diabetic nephropathy such as enlarged glomeruli with mesangial proliferation, basement membrane thickening, albuminuria and podocyte loss when aging. Insulin-like growth factor 1 receptor (Igf1R)- associated gene expression was regulated in TrkC-KO mice glomeruli by qPCR. Phosphoproteins associated with insulin, erb-b2 receptor tyrosine kinase (Erbb) and Toll-like receptor signaling were enriched in lysates of podocytes treated with the TrkC ligand neurotrophin-3(Nt-3) in a mass spectrometry analysis. Activation of TrkC by Nt-3 resulted in phosphorylation of the Igf1R on activating tyrosine residues in podocytes. Our results identify TrkC to be a potentially targetable mediator of diabetic nephropathy.
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2016-07-22 | E-GEOD-84663 | biostudies-arrayexpress
Project description:Comparing glomerular gene expression level between mice with different susceptibilities to diabetic nephropathy, DBA/2 (susceptible) and C57BL/6 (resistant) mice, respectively. The hypothesis is that differential expression of glomerular genes regulate susceptibility to diabetic nephropathy. The results show immune related genes. Thus, glomerular inflammation may increase susceptibility to diabetic nephropathy in mice.
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Project description:Albuminuria is significantly reduced following Roux-en-Y gastric bypass (RYGB) surgery, suggesting a renoprotective effect of the intervention. Herein, we assess the relative impact of RYGB and RYGB equivalent non-surgical weight loss and glycaemic improvement on glomerular injury and global renal transcriptomic responses in the Zucker diabetic fatty rat (ZDF) model of diabetic nephropathy. We coined the term "medical bypass" (MB) to describe the intensive diet and pharmacotherapy based non-surgical intervention Adult ZDF rats underwent sham surgery (n=15) or RYGB (n=9). Nine sham-operated rats were calorie restricted and received insulin, liraglutide, metformin, ramipril, rosuvastatin and fenofibrate for 2 months (MB). Zucker fa/+ rats acted as healthy controls throughout. Bodyweight, glycaemia, albuminuria and glomerular injury specifically podocyte number, density and ultrastructure were assessed at follow up. Renal transcriptomes were compared by RNA-seq. RYGB resulted in 20-30% weight loss, normalized glycaemia and albuminuria and reduced indices of glomerular injury, specifically podocyte injury (foot process effacement). RYGB equivalent outcomes were obtained on all parameters following MB.
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Project description:Podocyte injury in diabetic kidney disease contributes to the development of albuminuria and subsequent renal decline. Clinically, gastric bypass surgery is associated with reductions in albuminuria, and rodent studies demonstrate coherent improvements in renal histology. We aimed to investigate the mechanisms underpinning remission of albuminuria following gastric bypass focussing on podocyte injury. Firstly, we tracked the evolution of albuminuria and cognate evidence of histological and ultrastructural damage to the glomerulus in male Zucker Diabetic Fatty rats. Secondly, we examined the impact of gastric bypass in these rats, focussing on podocyte injury. Thirdly, we conducted a global transcriptomic study profiling the shift in the renal transcriptome in the Zucker Diabetic Fatty rats rat and its relevance to human disease. Lastly, we explored whether gastric bypass could reverse the changes seen in the disease associated transcriptome. Albuminuria in the Zucker Diabetic Fatty rat developed by 12 weeks of age. This was accompanied by glomerulomegaly, podocyte stress and ultrastructural evidence of podocyte dedifferentiation. When animals underwent gastric bypass at 12 weeks of age, marked reductions in albuminuria in association with normalisation of glomerular tuft size, attenuation of podocyte stress and improvements in podocyte foot process morphology were observed within 2 months of surgery. A characteristic disease associated gene expression signature was observed in the kidneys of Zucker Diabetic Fatty rats, with a core set of alterations conserved in global analysis of the human DKD transcriptome. Many of the shared gene expression alterations were reversed by gastric bypass. Reductions in podocyte injury represent a key mechanism underpinning the remission of albuminuria following gastric bypass.
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