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 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:Radix puerariae, a traditional Chinese herbal medication, has been used to treat patients with diabetic kidney disease (DKD). Our previous studies demonstrated that puerarin, the active compound of radix puerariae, improves diabetic podocyte injury in type 1 DKD mice through attenuation of oxidative stress. However, the direct molecular target of puerarin and its underlined mechanisms in DKD remains unknown. In this study, we first confirmed that puerarin also improved DKD in type 2 diabetic mice (db/db). Through RNA-sequencing of isolated glomeruli, we found that differentially expressed genes (DEGs) that were altered in the glomeruli of these diabetic mice but reversed by puerarin treatment were involved mostly in oxidative stress, inflammatory, and fibrosis. Further analysis of these reversed DEGs revealed protein kinase A (PKA) was among the top pathways. By utilizing the drug affinity responsive target stability (DARTS) method combined with mass spectrometry analysis we identified guanine nucleotide-binding protein Gi alpha-1 (Gnai1) as the direct binding partner of puerarin. Gnai1 is an inhibitor of cAMP production which is known to have protection against podocyte injury. Searching Nephroseq datasets revealed that Gnai1 expression increased in the glomeruli of human DKD. In vitro, we showed that puerarin not only interacted with Gnai1 but also increased cAMP production in human podocytes and kidney cortex of mice treated with peurarin. Puerarin also enhanced CREB phosphorylation, a downstream transcription factor of cAMP/PKA. Overexpression of CREB reduced high glucose-induced podocyte apoptosis. We conclude that the renal protective effects of puerarin are likely through inhibiting Gnai1 to activate cAMP/PKA/CREB pathway in podocytes.
2022-02-15 | GSE196780 | GEO
Project description:Cellular senescence is associated with the progression of diabetic kidney disease (DKD), and accelerated podocyte senescence promotes the pathogenesis of renal damage. We found that GPR124 was reduced in cultured human podocytes treated with high glucose (HG).To further clarify the role of GPR124 in podocytes, we overexpressed GPR124 via plasmid-harboring adenovirus infection. By RNA sequencing analysis of podocytes with different treatment, we observed GPR124 overexpression significantly affected several kinds of cell adhesion.
2024-11-05 | GSE280773 | GEO
Project description:Sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is a lipid raft enzyme that regulates plasma membrane (PM) fluidity. Here we report that SMPDL3b excess, as observed in podocytes in diabetic kidney disease (DKD), impairs insulin receptor isoform B-dependent pro-survival insulin signaling by interfering with insulin receptor isoforms binding to caveolin-1 in PM. SMPDL3b excess affects the production of active sphingolipids resulting in decreased ceramide-1-phosphate (C1P) content as observed in human podocytes in vitro and in kidney cortexes of diabetic db/db mice in vivo. Podocyte-specific Smpdl3b deficiency in db/db mice is sufficient to restore kidney cortex C1P content and to protect from DKD. Exogenous administration of C1P restores IR signaling in vitro and prevents established DKD progression in vivo. Taken together, we identified SMPDL3b as a modulator of insulin signaling and demonstrated that supplementation with exogenous C1P may represent a lipid therapeutic strategy to treat diabetic complications such as DKD.
2019-04-12 | GSE129666 | GEO