Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA341474 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Overexpression of glomerular JAK2 mRNA specifically in glomerular podocytes of 129S6 mice led to significant increases in albuminuria, mesangial expansion, glomerulosclerosis, glomerular fibronectin accumulation, and glomerular basement membrane thickening as well as a significant reduction in podocyte density in diabetic mice. Treatment with a specific JAK1/2 inhibitor partly reversed the major phenotypic changes of DKD
2017-07-31 | GSE86317 | GEO
Project description:We compared mRNA profiles of isolated glomeruli versus sorted podocytes between diabetic and control mice. IRG mice crossed with eNOS-/- mice were further bred with podocin-rTTA and TetON-Cre mice to permanently label podocytes before the diabetic injury. Diabetes was induced by injection of streptozotocin. mRNA profiles of isolated glomeruli and sorted podocytes from diabetic and control mice at 10 weeks after induction of diabetes were examined. Consistent with the previous reports, expression of podocyte-specific markers in the glomeruli were down-regulated in the diabetic mice compared to controls. However, these differences disappeared when mRNA levels were corrected for podocyte number per glomerulus. Interestingly, the expression of these markers was not altered in sorted podocytes from diabetic mice, suggesting that the reduced expression of podocyte markers in isolated glomeruli is likely a secondary effect of reduced podocyte number, rather than the loss of differentiation markers. Analysis of the differentially expressed genes in diabetic mice also revealed distinct up-regulated pathways in the glomeruli (mitochondrial function and oxidative stress) and podocytes (actin organization). In conclusion, our data suggest that podocyte-specific gene expression in transcriptome obtained from the whole glomeruli may not represent those of podocytes in the diabetic kidney. We compared mRNA profiles of isolated glomeruli versus sorted podocytes between diabetic and control mice.
2016-03-16 | E-GEOD-79291 | biostudies-arrayexpress
Project description:We compared mRNA profiles of isolated glomeruli versus sorted podocytes between diabetic and control mice. IRG mice crossed with eNOS-/- mice were further bred with podocin-rTTA and TetON-Cre mice to permanently label podocytes before the diabetic injury. Diabetes was induced by injection of streptozotocin. mRNA profiles of isolated glomeruli and sorted podocytes from diabetic and control mice at 10 weeks after induction of diabetes were examined. Consistent with the previous reports, expression of podocyte-specific markers in the glomeruli were down-regulated in the diabetic mice compared to controls. However, these differences disappeared when mRNA levels were corrected for podocyte number per glomerulus. Interestingly, the expression of these markers was not altered in sorted podocytes from diabetic mice, suggesting that the reduced expression of podocyte markers in isolated glomeruli is likely a secondary effect of reduced podocyte number, rather than the loss of differentiation markers. Analysis of the differentially expressed genes in diabetic mice also revealed distinct up-regulated pathways in the glomeruli (mitochondrial function and oxidative stress) and podocytes (actin organization). In conclusion, our data suggest that podocyte-specific gene expression in transcriptome obtained from the whole glomeruli may not represent those of podocytes in the diabetic kidney.
2016-03-16 | GSE79291 | GEO
Project description:Transcriptome of mice kidney with diabetic kidney disease
| PRJNA675958 | ENA
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.
2021-09-10 | PXD017960 | Pride
Project description:Podocyte injury is involved in the onset and progression of various kidney diseases. We previously demonstrated that the transcription factor, old astrocyte specifically induced substance (OASIS) in myofibroblasts, contributes to kidney fibrosis, as a novel role of OASIS in the kidneys. Importantly, we found that OASIS is also expressed in podocytes; however, the pathophysiological significance of OASIS in podocytes remains unknown. Upon lipopolysaccharide (LPS) treatment, there is an increase in OASIS in murine podocytes. Enhanced serum creatinine levels and tubular injury, but not albuminuria and podocyte injury, are attenuated upon podocyte-restricted OASIS knockout in LPS-treated mice, as well as diabetic mice. The protective effects of podocyte-specific OASIS deficiency on tubular injury are mediated by protein kinase C iota (PRKCI/PKCι), which is negatively regulated by OASIS in podocytes. Furthermore, podocyte-restricted OASIS transgenic mice show tubular injury and tubulointerstitial fibrosis, with severe albuminuria and podocyte degeneration. Finally, there is an increase in OASIS-positive podocytes in the glomeruli of patients with minimal change nephrotic syndrome and diabetic nephropathy. Taken together, OASIS in podocytes contributes to podocyte and/or tubular injury, in part through decreased PRKCI. The induction of OASIS in podocytes is a critical event for the disturbance of kidney homeostasis.
2022-06-22 | GSE206525 | GEO
Project description:Podocyte dysfunction is considered as the main contributor to the development and progression of diabetic kidney disease(DKD).High glucose(HG)or advanced glycation end products (AGEs) can lead to podocyte dysfunction.To explore the the molecular mechanism of podocyte dysfunction, we screened the mRNA expression profiles of podocytes treated with HG(50mmol/L)and AGEs(400µg/mL) through transcriptomics.
2024-12-31 | GSE236426 | GEO
Project description:Podocyte injury is a major determinant in proteinuric kidney disease and identification of potential therapeutic targets for preventing podocyte injury has clinical importance. Here, we show that histone deacetylase Sirt6 protects against podocyte injury through epigenetic regulation of Notch signaling. Sirt6 is downregulated in renal biopsies from patients with podocytopathies and its expression negatively correlates withglomerular filtration rate. Podocyte-specific deletion of Sirt6 exacerbates podocyte injury and proteinuria in two independent mouse models including diabetic nephropathy and adriamycin-induced nephropathy. Sirt6 has pleiotropic protective actions in podocytes including anti-inflammatory and anti-apoptotic effects, is involved in actin cytoskeleton maintenance, and promotes autophagy. Sirt6 also reduces urokinase plasminogen activator receptor expression, which is a key factor for podocyte foot process effacement and proteinuria. Mechanistically, Sirt6 inhibits Notch1 and Notch4 transcription by deacetylating the histone H3K9. We suggest Sirt6 as a potential therapeutic target in proteinuric kidney disease.
2017-06-20 | GSE100185 | GEO
Project description:Diabetic kidney disease (DKD) is the leading cause of progressive chronic kidney disease in adults in the United States. However, the impact of preterm birth on the progression of DKD has not been studied. The goal of this project is to determine the effect of preterm birth on kidney health in a diabetic mouse model. CD-1 pups born preterm (19 days post conception (dpc)) and term (20 dpc) were studied, and outcomes of the male mice were reported, all compared to term mice. Preterm and term mice were treated with streptozotocin at six weeks to induce hyperglycemia. Body weight and blood sugar were monitored. Histologic, molecular, and imaging techniques were used to characterize the mice at 18 weeks. The preterm mice with diabetes had a lower podocyte density, lower proximal tubular fraction, and more atubular glomeruli compared to the term mice without diabetes. They also had a lower podocyte density and lower renin expression compared to term mice with diabetes. Based on single-cell RNA sequencing, preterm mice with diabetes had increased expression of genes related to the angiogenesis migration pathway-related in endothelial cells and increased expression of genes in the actin adhesion pathway in podocytes compared to term mice with diabetes. Furthermore, the preterm mice with diabetes exhibited a weaker endothelial cell-podocyte interaction compared to term mice with diabetes. These data suggest that preterm birth increases susceptibility to glomerular and tubular damage after a brief “second hit” of hyperglycemia. In conclusion, preterm birth disrupts endothelial-podocyte crosstalk and increases susceptibility to kidney injury induced by hyperglycemia.
2025-06-04 | GSE280780 | GEO
Project description:Diabetic kidney disease (DKD) is the leading cause of progressive chronic kidney disease in adults in the United States. However, the impact of preterm birth on the progression of DKD has not been studied. The goal of this project is to determine the effect of preterm birth on kidney health in a diabetic mouse model. CD-1 pups born preterm (19 days post conception (dpc)) and term (20 dpc) were studied, and outcomes of the male mice were reported, all compared to term mice. Preterm and term mice were treated with streptozotocin at six weeks to induce hyperglycemia. Body weight and blood sugar were monitored. Histologic, molecular, and imaging techniques were used to characterize the mice at 18 weeks. The preterm mice with diabetes had a lower podocyte density, lower proximal tubular fraction, and more atubular glomeruli compared to the term mice without diabetes. They also had a lower podocyte density and lower renin expression compared to term mice with diabetes. Based on single-cell RNA sequencing, preterm mice with diabetes had increased expression of genes related to the angiogenesis migration pathway-related in endothelial cells and increased expression of genes in the actin adhesion pathway in podocytes compared to term mice with diabetes. Furthermore, the preterm mice with diabetes exhibited a weaker endothelial cell-podocyte interaction compared to term mice with diabetes. These data suggest that preterm birth increases susceptibility to glomerular and tubular damage after a brief “second hit” of hyperglycemia. In conclusion, preterm birth disrupts endothelial-podocyte crosstalk and increases susceptibility to kidney injury induced by hyperglycemia.
2025-06-04 | GSE280781 | GEO