Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Podocyte Epac1 promotes glycolysis and protects against glomerulonephritis

ABSTRACT: Podocyte Epac1 promotes glycolysis and protects against glomerulonephritis

PROVIDER: PRJNA993701 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR25238468.fastq.gz	Fastqsanger.gz
	SRR25238469.fastq.gz	Fastqsanger.gz
	SRR25238470.fastq.gz	Fastqsanger.gz
	SRR25238471.fastq.gz	Fastqsanger.gz
	SRR25238472.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 21

Similar Datasets

Podocyte Epac1 promotes glycolysis and protects against glomerulonephritis

Project description:The second messenger cyclic AMP (cAMP) is involved in many aspects of renal physiology and disease. Epac is an effector of cAMP and its pathophysiological role in the development of chronic kidney diseases (CKD) has yet to be determined. Here, we show that total Epac1 isoform genetic deletion does not cause any baseline renal abnormalities but remarkably potentiates the deterioration of renal structure and function during the progression of the nephrotoxic serum (NTS)-induced glomerular nephritis (GN). Similarly, podocyte Epac1 deletion in podocytes exacerbated GN development. Global gene expression profile in mouse glomeruli using RNAseq analysis indicates a transcriptomic signature of GN related to immune system, extracellular matrix, and cytoskeleton gene dysregulation at the onset of the disease. Furthermore, glomeruli with podocyte Epac1 deletion display altered mitochondrion and metabolic processes in nephritic mice. Consistently, mechanistic analysis demonstrates that Epac1 activation increases human podocyte mitochondrial function to cope with extra energy demand in stress condition. Of particular importance, Epac1 increases aerobic glycolysis to ameliorate podocyte viability and motility. Therefore, the metabolic flexibility mediated by Epac1 constitutes a protective mechanism against podocyte injury. Altogether these data highlight the potential of Epac1 as a therapeutic approach for CKD treatment.

2024-06-10 | GSE237097 | GEO

GPR124 Protects against Podocyte Senescence and Injury in Diabetic Kidney Disease

Project description:GPR124 Protects against Podocyte Senescence and Injury in Diabetic Kidney Disease

| PRJNA1180511 | ENA

Reversible SAHH inhibitor protects against glomerulonephritis in lupus-prone NZB/NZW F1 mice by modulating α-actinin-4 associated skeleton organization of podocytes

Project description:Glomerulonephritis is one of the major complications and causes of death in systemic lupus erythematosus (SLE). Podocytes can be injured in many forms of glomerular disease, characteristic changes are actin cytoskeleton reorganization of involved foot process. ACTN4, encodes α-actinin-4, an actin-binding and crosslinking protein localized to podocytes in renal glomerulus. Abnormal expression of α-actinin-4 in mice leads to proteinuria and podocyte damage. DZ2002, a reversible S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor with immunosuppressive properties and potent therapeutic activity against various autoimmune diseases in mice. Here, we found that DZ2002 could significantly ameliorate nephritis of lupus-prone mice. Our results showed that DZ2002 decreased the accumulation of α-actinin-4, inhibited expression of integrin-linked kinase and downstream phosphorylation of β1-integrin.

2019-11-12 | PXD010059 | Pride

Sirt6 Deficiency Exacerbates Podocyte Injury and Proteinuria through Targeting Notch Signaling

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

GPR124 Protects against Podocyte Senescence and Injury in Diabetic Kidney Disease

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

PIK3CA inhibition in models of proliferative glomerulonephritis and lupus nephritis

Project description:Proliferative glomerulonephritis is a severe condition often leading to kidney failure. There is a significant lack of effective treatment for these disorders. Here, following the identification of a somatic PIK3CA gain-of-function mutation in podocytes of a patient, we demonstrate using multiple genetically engineered mouse models, single-cell RNA sequencing and spatial transcriptomics the crucial role played by this pathway for proliferative glomerulonephritis development by promoting podocyte proliferation, dedifferentiation and inflammation. Additionally, we show that alpelisib, a PI3Kα inhibitor, improves glomerular lesions and kidney function in different mouse models of proliferative glomerulonephritis and lupus nephritis by targeting podocytes. Surprisingly, we determined that pharmacological inhibition of PI3Kα affects B and T lymphocyte population in lupus nephritis mouse models with decrease in the production of proinflammatory cytokines, autoantibodies and glomerular complement deposition, which are all characteristic features of PI3K delta (PI3Kδ) inhibition, the primary PI3K isoform expressed in lymphocytes. Importantly, PI3Kα inhibition does not impact lymphocyte function under normal conditions. These findings were then confirmed in human lymphocytes isolated from patients with active lupus nephritis. In conclusion, we demonstrate the major role played by PI3Kα in proliferative glomerulonephritis and show that in this condition, alpelisib acts on both podocytes and the immune system.

2024-06-10 | GSE263909 | GEO

Human podocyte differentiation

Project description:Microarray analysis of the molecular phenotype of the glomerular podocyte during temperature shift-induced differentiation Keywords = glomerular podocyte Keywords = differentiation

2010-05-26 | E-GEOD-1545 | biostudies-arrayexpress

Tristetraprolin expression by keratinocytes protects against skin carcinogenesis

Project description:Tristetraprolin expression by keratinocytes protects against skin carcinogenesis

| PRJNA636408 | ENA

KDM4B epigenetically protects against obesity and metabolic dysfunction

Project description:KDM4B epigenetically protects against obesity and metabolic dysfunction

| PRJNA397224 | ENA

Swc4 protects chromatin against genome instability and aneuploidy

Project description:Swc4 protects chromatin against genome instability and aneuploidy

| PRJNA778198 | ENA