Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Immune-complex activated gasdermin D facilitates mitochondrial DNA membrane translocation and extracellular release in systemic lupus erythematous [RNA-Seq]

ABSTRACT: The purpose of this study was to study the roles of GSDMD in systemic lupus erythematous. Here, we used RNA sequencing from wild type, Pristane induced wild type and Pristane induced GSDMD knockout mice to detect changes in transcriptomes of kidneys.

ORGANISM(S): Mus musculus

PROVIDER: GSE173767 | GEO | 2021/11/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Immune-complex activated gasdermin D facilitates mitochondrial DNA membrane translocation and extracellular release in systemic lupus erythematous [RNA-Seq]

Project description:Immune-complex activated gasdermin D facilitates mitochondrial DNA membrane translocation and extracellular release in systemic lupus erythematous [RNA-Seq]

| PRJNA726985 | ENA

Retinoic acid exerts disease stage-dependent effects on pristane-induced lupus

Project description:We previously showed that all-trans-retinoic acid (tRA), an active metabolite of vitamin A, exacerbated pre-existing autoimmunity in lupus; however, its effects before the development of autoimmunity are unknown. Here, using a pristane-induced model, we show that tRA exerts differential effects when given at the initiation vs. continuation phase of lupus. Unlike tRA treatment during active disease, pre-pristane treatment with tRA aggravated glomerulonephritis through increasing renal expression of pro-fibrotic protein laminin β1, activating bone marrow conventional dendritic cells (cDCs), and upregulating the interaction of ICAM-1 and LFA-1 in the spleen indicating an active process of leukocyte activation and trafficking. Transcriptomic analysis revealed that prior to lupus induction, tRA significantly upregulated the expression of genes associated with cDC activation and migration. Post-pristane tRA treatment, on the other hand, did not significantly alter the severity of glomerulonephritis; rather, it exerted immunosuppressive functions of decreasing circulatory and renal deposition of autoantibodies as well as suppressing the renal expression of proinflammatory cytokines and chemokines. Together, these findings suggest that tRA differentially modulate lupus-associated kidney inflammation depending on the time of administration. Interestingly, both pre- and post-pristane treatments with tRA reversed pristane-induced leaky gut and modulated the gut microbiota in a similar fashion, suggesting a gut microbiota-independent mechanism by which tRA affects the initiation vs. continuation phase of lupus.

2020-02-19 | GSE140104 | GEO

Whole blood gene expression profiles from a lupus nephritis mouse model: SNF1 (SWR X NZB F1) mice treated with pristane

Project description:We characterized the longitudinal gene expression profiles of whole blood from a novel lupus model nephritis: SNF1 (SWR X NZB F1) mice treated with pristane. Genes from interferon, plasma cell, neutrophil, T-cell and protein synthesis signatures were differentially expressed in the pristane-SNF1 model compared to the untreated matched control animals.

2016-09-06 | GSE86424 | GEO

The Card19 locus regulates apoptosis and pyroptosis downstream of caspase activation and gasdermin D cleavage independently from IL-1 cytokine release

Project description:Cell death plays a critical role in inflammatory responses. During pyroptosis, inflammatory caspases cleave Gasdermin D (GSDMD) to release an N-terminal fragment that generates plasma membrane pores that mediate cell lysis and IL-1 release. However, certain stimuli and cell types release IL-1 cytokines through GSDMD pores in cells that remain viable, a process termed hyperactivation. How these distinct cell fate choices are regulated downstream of GSDMD pore formation is unknown. Here, we demonstrate that the Card19 locus promotes lysis downstream of caspase activation. Despite being largely protected from cell death, CARD19-deficient macrophages had no defect in caspase activation, IL-1 secretion, or GSDMD cleavage. CARD19, a mitochondrial protein, was not responsible for the observed phenotypes, nor was the recently identified pore forming protein NINJ1 which regulates terminal pore formation during multiple forms of cell death. Furthermore, previously identified cell death phenotypes attributed to Sterile alpha and heat Armadillo motif-containing protein (SARM) were revealed to be caused by a passenger mutation. Importantly, Card19-/ mice had increased susceptibility to Yersinia infection, including increased mortality, higher bacterial burdens and pronounced splenomegaly. These findings implicate the Card19 locus as a factor that couples caspase processing and GSDMD cleavage to cell death, providing insight into how the checkpoint between hyperactivation and cell death is regulated.

2021-03-21 | GSE168489 | GEO

Gasdermin D deficiency affects mitochondrial dynamics and metabolic to orchestrates neurogenesis during embryonic development

Project description:Purpose: To gain futher insight into how GSDMD regulates the proliferative of neural progenitors ,RNA-seq was used to analyze the genome-wide changes resulting from the cerebral cortices of E13 GSDMD conditional knock out mice and littermate wild-type. Methods: Total RNA from E13 telencephalic tissue of wild-type(WT) and Gsdmdfl/fl;Nestin-Cre mice was extracted. Specifically, Agilent 2100 Bioanalyze was used to quality controlled and quantified. then, total RNA was converted to cDNA and bound the library. RNA-sequencing analysis was used by the Illumina HiSeq 2500 platform in Annoroad Genomics Results: Approximately one thousand transcripts showed differential expression between the wild-type(WT) and Gsdmdfl/fl;Nestin-Cre mice brain cortex, with a fold change ≥1.5 and p value <0.05.Geneontology analysis of the up-regulated genes showed obvious enrichment of biological processes related to development and proliferation.The down-regulated genes exhibited enrichment of biological processes related to the negative regulation of cell proliferation and developmental process. These results reflected GSDMD plays a role in cortex development. Conclusions: RNA-seq based transcriptome characterization would provide a overall understanding how GSDMD gene contribute to brain cortical development.

2023-11-13 | GSE247326 | GEO

Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway

Project description:The process of pyroptosis is mediated by inflammasomes and a downstream effector known as gasdermin D (GSDMD). Upon cleavage by inflammasome-associated caspases, the N-terminal domain of GSDMD forms membrane pores that promote cytolysis. Numerous proteins promote GSDMD cleavage, but none are known to be required for pore formation after GSDMD cleavage. Herein, we report a forward genetic screen that identified the Ragulator-Rag complex as being necessary for GSDMD pore formation and pyroptosis in macrophages. Mechanistic analysis revealed that Ragulator-Rag is not required for GSDMD cleavage upon inflammasome activation, but rather promotes GSDMD oligomerization in the plasma membrane. Defects in GSDMD oligomerization and pore formation can be rescued by mitochondrial poisons that stimulate reactive oxygen species (ROS) production, and ROS modulation impacts the ability of inflammasome pathways to promote pore formation downstream of GSDMD cleavage. These findings reveal an unexpected link between key regulators of immunity (inflammasome-GSDMD) and metabolism (Ragulator-Rag).

2021-06-29 | GSE179089 | GEO

Gasdermin D inhibition confers antineutrophil mediated cardioprotection in acute myocardial infarction

Project description:Acute myocardial infarction (AMI) induces blood leukocytosis, which correlates inversely with patient survival. The molecular mechanisms leading to leukocytosis, and recruitment to the infarcted heart, remain poorly understood. Using an AMI mouse model, gasdermin D (GSDMD) was identified in activated neutrophils early in AMI. We demonstrated that GSDMD is required for enhanced recruitment of neutrophils and monocytes to the infarcted heart. Loss of GSDMD resulted in reduced release of IL-1β from neutrophils and reduced recruitment of neutrophils and monocytes to the infarcted heart. Knockout of GSDMD in mice significantly reduced infarct size, improved cardiac function and increased survival post AMI. Through a series of bone marrow transplantation studies and leukocytes depletion experiments, we further demonstrated that excessive bone marrow derived and GSDMD-dependent neutrophil recruitment, contributes to the detrimental immunopathology after AMI. Pharmacological inhibition of GSDMD also conferred cardioprotection post AMI, through reduction of scar size and enhancement of heart function. Our study provides new mechanistic insights into molecular regulation of neutrophil generation and recruitment after AMI, and supports GSDMD as a new target for improved ventricular remodeling and reduced heart failure after AMI.

2022-01-05 | GSE181872 | GEO

Kidney gene expression profiles from a lupus nephritis mouse model: SNF1 (SWR X NZB F1) mice treated with pristane

Project description:We characterized the longitudinal gene expression profiles of kidneys from a novel lupus model nephritis: SNF1 (SWR X NZB F1) mice treated with pristane. Genes from biological processes such as IFN response, complement, Fc gamma receptors, immune recruitment, innate immune pattern recognition, antibody response and fibrosis,were upregulated in diseased kidneys.

2016-09-06 | GSE86425 | GEO

NCF1-dependent low production of reactive oxygen species in plasmacytoid dendritic cells exacerbates lupus

Project description:Low capacity to produce reactive oxygen species (ROS) due to mutations in neutrophil cytosolic factor 1 (NCF1/p47phox) is strongly associated with lupus development both in humans and mouse models. Here, we aim to identify the major mechanisms of the Ncf1-disease association. We found that plasmacytoid dendritic cells (pDCs), the most potent producers of type I IFNs, exacerbate pristane-induced lupus in ROS-defective Ncf1-mutant and human NCF1-339 variant carrying mice. ROS deficiency in mouse models with Ncf1 mutation or human NCF1-339 variant leads to enhanced pDC generation via the TLR7/AKT/mTOR pathway and accumulation at sites of inflammation, resulting in an increased IFNα secretion. The produced IFNα further stimulates the JAK1/STAT1 pathway, which we found is hyperreactive in ROS-deficient pDCs. This, in turn, leads to increased type I IFN signature and enhanced proinflammatory responses. Our discoveries explain the causative effect of dysfunctional Ncf1 and pathogenicity of pDCs in lupus.

2023-03-12 | PXD035964 | Pride

Project description:GSDMD promtes innate and adaptive immunity in the kidney of pristane-induced lupus mouse

| PRJNA723994 | ENA

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data