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:Podocyte injury is a critical early event in the progression of diabetic kidney disease (DKD), and metabolic reprogramming has emerged as a key determinant of podocyte dysfunction. Although podocytes rely predominantly on glycolysis to maintain their structural and functional integrity, the molecular regulators controlling glycolytic flux in podocytes during DKD remain incompletely understood. Here, we demonstrated that pancreatic progenitor cell differentiation and proliferation factor (PPDPF) was significantly reduced in podocytes from both DKD patients and diabetic mice. Podocyte-specific deletion of PPDPF in mice aggravated albuminuria, glomerular injury, and podocyte injury under diabetic conditions. However, overexpression of PPDPF ameliorated cytoskeletal disorganization and foot process effacement through increasing glycolytic flux and ATP production. Mechanistically, PPDPF competitively bound to WW Domain-containing E3 Ubiquitin Protein Ligase 1 (WWP1) and suppressed WWP1-mediated ubiquitination and degradation of CCCTC-binding factor (CTCF), thereby sustaining phosphoglycerate mutase 1 (PGAM1) transcription and promoting podocyte glycolysis. Notably, PPDPF expression was associated with podocyte loss, serum creatinine and glomerular filtration rate in patients with DKD. Thus, our findings identified PPDPF as a previously unrecognized guardian of podocyte glycolysis and suggest that targeting the PPDPF-dependent metabolic pathway may represent a promising therapeutic strategy for DKD.
2026-09-08 | GSE342320 | 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:The m6A modification, a prevalent epigenetic change, is implicated in various disease processes. Our previous research has revealed METTL3 abnormal expression in aging kidney tissues, correlating with its role in regulating renal fibrosis. In this study, we aim to create a conditional METTL3 knockout model to delve deeper into its regulatory mechanisms in diabetic kidney disease (DKD).Utilizing a conditional, podocyte-specific METTL3 knockout mouse model induced by STZ and transfected mouse podocytes with siMETTL3 plasmids stimulated by advanced glycation end products (AGEs) in vitro, we aim to investigate potential associations between podocyte mitotic catastrophe, the release of inflammatory factors, and diabetic kidney injury. Our focus extends to unraveling the role of METTL3/IGF2BP2 in m6A modification, particularly through MDM2 degradation.Elevated m6A levels were evident in renal tissues of type I diabetic mice and in cultured mouse podocytes exposed to AGEs, attributed to increased METTL3 expression. Podocyte-specific METTL3 knockdown significantly mitigated podocyte injury in STZ-induced diabetic mice, leading to reduced albuminuria and diminished renal pathology. Mechanistically, METTL3 induces abnormal m6A modifications sites of MDM2, triggering subsequent degradation through IGF2BP2 dependent way. Consequently, this abnormal m6A regulation instigates increased MDM2 expression, activating the Notch signaling pathway, prompting podocyte cell cycle re-entry in diabetic conditions, releasing inflammatory factors, and inducing dedifferentiation of podocytes.The aberrant m6A modification, mediated by METTL3, stands pivotal effect of podocytes during diabetic condition. Targeting m6A via METTL3, the writer enzyme, may offer a potential avenue for treating DKD.
2026-05-19 | GSE260730 | 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.
2016-03-16 | GSE79291 | GEO
Project description:Transcriptome of mice kidney with diabetic kidney disease
| PRJNA675958 | ENA
Project description:Podocyte dysfunction represents both an early pathological hallmark and a key driver of proteinuria in diabetic kidney disease (DKD); however, the epigenetic mechanisms underlying this process remains poorly defined. Here, we identify the histone methyltransferase SETDB2 as a pivotal epigenetic suppressor of podocyte dysfunction and DKD progression. Glomerular SETDB2 expression is markedly reduced in both DKD patients and mouse models, showing an inverse correlation with disease severity. Podocyte-specific SETDB2 deficiency exacerbates podocytes dysfunction and accelerates DKD progression, whereas its overexpression exerts renal protective effects. Mechanistically, SETDB2 directly enhances H3K9 trimethylation at the Smad3 promoter, thereby repressing SMAD3 expression and activation, ultimately preserving podocyte function. Notably, we identify TCF21, a transcription factor downregulated in DKD, as a direct upstream regulator of Setdb2 expression via promoter binding and transcriptional activation. Collectively, these findings establish SETDB2 as a key regulator of podocyte integrity and a promising therapeutic target for DKD.
2026-07-31 | GSE303885 | GEO
Project description:Podocyte dysfunction represents both an early pathological hallmark and a key driver of proteinuria in diabetic kidney disease (DKD); however, the epigenetic mechanisms underlying this process remains poorly defined. Here, we identify the histone methyltransferase SETDB2 as a pivotal epigenetic suppressor of podocyte dysfunction and DKD progression. Glomerular SETDB2 expression is markedly reduced in both DKD patients and mouse models, showing an inverse correlation with disease severity. Podocyte-specific SETDB2 deficiency exacerbates podocytes dysfunction and accelerates DKD progression, whereas its overexpression exerts renal protective effects. Mechanistically, SETDB2 directly enhances H3K9 trimethylation at the Smad3 promoter, thereby repressing SMAD3 expression and activation, ultimately preserving podocyte function. Notably, we identify TCF21, a transcription factor downregulated in DKD, as a direct upstream regulator of Setdb2 expression via promoter binding and transcriptional activation. Collectively, these findings establish SETDB2 as a key regulator of podocyte integrity and a promising therapeutic target for DKD.
2026-07-31 | GSE303884 | GEO
Project description:Podocyte dysfunction represents both an early pathological hallmark and a key driver of proteinuria in diabetic kidney disease (DKD); however, the epigenetic mechanisms underlying this process remains poorly defined. Here, we identify the histone methyltransferase SETDB2 as a pivotal epigenetic suppressor of podocyte dysfunction and DKD progression. Glomerular SETDB2 expression is markedly reduced in both DKD patients and mouse models, showing an inverse correlation with disease severity. Podocyte-specific SETDB2 deficiency exacerbates podocytes dysfunction and accelerates DKD progression, whereas its overexpression exerts renal protective effects. Mechanistically, SETDB2 directly enhances H3K9 trimethylation at the Smad3 promoter, thereby repressing SMAD3 expression and activation, ultimately preserving podocyte function. Notably, we identify TCF21, a transcription factor downregulated in DKD, as a direct upstream regulator of Setdb2 expression via promoter binding and transcriptional activation. Collectively, these findings establish SETDB2 as a key regulator of podocyte integrity and a promising therapeutic target for DKD.
2026-07-31 | GSE303883 | GEO
Project description:Podocyte dysfunction represents both an early pathological hallmark and a key driver of proteinuria in diabetic kidney disease (DKD); however, the epigenetic mechanisms underlying this process remains poorly defined. Here, we identify the histone methyltransferase SETDB2 as a pivotal epigenetic suppressor of podocyte dysfunction and DKD progression. Glomerular SETDB2 expression is markedly reduced in both DKD patients and mouse models, showing an inverse correlation with disease severity. Podocyte-specific SETDB2 deficiency exacerbates podocytes dysfunction and accelerates DKD progression, whereas its overexpression exerts renal protective effects. Mechanistically, SETDB2 directly enhances H3K9 trimethylation at the Smad3 promoter, thereby repressing SMAD3 expression and activation, ultimately preserving podocyte function. Notably, we identify TCF21, a transcription factor downregulated in DKD, as a direct upstream regulator of Setdb2 expression via promoter binding and transcriptional activation. Collectively, these findings establish SETDB2 as a key regulator of podocyte integrity and a promising therapeutic target for DKD.
2026-07-31 | GSE303915 | GEO