RNA-Sequencing Analysis of of heart tissue from murine model of endotoxemia
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE215131 | GEO | 2025/10/10
REPOSITORIES: GEO
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Project description:The circulating proteome offers insight into the stage and severity of the immune response. To characterise the release kinetics and cellular source of plasma protein changes, serial samples were obtained from healthy volunteers (n=10, 3 time-points) injected with low-dose endotoxin (LPS) and analysed using date-independent acquisition (DIA) MS. The systemic and vascular inflammatory responses were compared using LPS-induced endotoxemia models in mice.
2021-02-11 | PXD021077 | Pride
Project description:Liver has a crucial role in the regulation of immune defense in systemic infections. During endotoxemia, the liver transits from an immune-tolerant towards an immune-active state and forms the first line of defense against invading microorganisms. the role of liver nonparenchymal cells in endotoxemia remains unintelligible. To characterize the liver nonparenchymal cells in endotoxemia liver, we performed single-cell RNA sequencing of liver nonparenchymal cells from healthy C57BL/6J mice and murine model of endotoxemia at early or late stage. The single-cell RNA-seq analyses revealed the heterogeneity of liver nonparenchymal cells in endotoxemia liver.
2023-02-28 | GSE186558 | GEO
Project description:Liver has a crucial role in the regulation of immune defense in systemic infections. During endotoxemia, the liver transits from an immune-tolerant towards an immune-active state and forms the first line of defense against invading microorganisms. the role of liver parenchymal cells in endotoxemia remains unintelligible. To characterize the liver parenchymal cells in endotoxemia liver, we performed single-cell RNA sequencing of liver parenchymal cells from healthy C57BL/6J mice and murine model of endotoxemia at early or late stage. The single-cell RNA-seq analyses revealed the heterogeneity of liver parenchymal cells in endotoxemia liver.
2022-04-06 | GSE186554 | GEO
Project description:Preterm neonates die at a significantly higher rate from sepsis than full-term neonates, attributable to their dysregulated immune response. In addition to tissue destruction caused directly by bacterial invasion, an overwhelming cytokine response by the immune cells to bacterial antigens also results in collateral damage. Sepsis leads to decreased gene expression of a critical transcription factor, Kruppel-like factor-2 (KLF2), a tonic repressor of myeloid cell activation. KLF2 gene expression is also lower in murine pups at an earlier postnatal age. Using a murine model of myeloid-KLF2 deletion, we show that loss of KLF2 leads to decreased survival after endotoxemia in a developmentally dependent manner, with increased mortality at postnatal day 4 (P4) compared to P12 pups. This survival is significantly increased by neutrophil depletion before endotoxemia. P4 knockout pups have increased pro-inflammatory cytokine levels after endotoxemia compared to P4 controls or P12 pups, with significantly increased levels of IL-1b, an end product of the activation of the NLRP3 inflammasome complex. Both loss of myeloid KLF2 and a younger postnatal age lead to increased NLRP3 protein expression and release of IL-1b in bone marrow neutrophils. Inhibition of NLRP3 inflammasome activation by MCC950 significantly increased survival after endotoxemia in P4 pups. Transcriptomic analysis of bone marrow neutrophils showed that loss of myeloid-KLF2 is associated with gene enrichment of pro-inflammatory pathways in a developmentally dependent manner. These data suggest that targeting KLF2 could be a novel strategy to decrease the pro-inflammatory cytokine storm in neonatal sepsis and improve survival in neonates with sepsis.
2025-03-10 | GSE278604 | GEO
Project description:Neutrophil KLF2 regulates inflammasome-dependent neonatal mortality from endotoxemia
| PRJNA1168073 | ENA
Project description:Polymorphonuclear cells (neutrophils) play an important role in the systemic inflammatory response syndrome and the development of sepsis. These cells are essential for the defense against microorganisms, but may also cause tissue damage. Therefore, neutrophil numbers and activity are considered to be tightly regulated. Previous studies have investigated gene transcription during experimental endotoxemia in whole blood and peripheral blood mononuclear cells. However, the gene transcription response of the circulating pool of neutrophils to systemic inflammatory stimulation in vivo is currently unclear. We examined neutrophil gene transcription kinetics in healthy human subjects (n=4) administered a single dose of endotoxin (LPS, 2 ng/kg iv). In addition, freshly isolated neutrophils were stimulated ex vivo with LPS, TNFM-NM-1, G-CSF and GM-CSF to identify stimulus-specific gene transcription responses. Whole transcriptome microarray analysis of circulating neutrophils at 2, 4 and 6 hours after LPS infusion revealed activation of inflammatory networks which are involved in signaling of TNFM-NM-1 and IL-1M-NM-1 and IL-1M-NM-2. The transcriptome profile of inflammatory activated neutrophils in vivo reflects extended survival and regulation of inflammatory responses. We show that these changes in neutrophil transcriptome are most likely due to a combination of early activation of circulating neutrophils by TNFM-NM-1 and G-CSF and a mobilization of young neutrophils from the bone marrow. After LPS infusion blood was taken at t=0, t=2, t=4 and t=6 hours. Neutrophils were isolated and gene expression of these cells was assessed. T=2, t=4 and t=6 were related to t=0 as control condition
2012-06-04 | E-GEOD-35590 | biostudies-arrayexpress
Project description:Polymorphonuclear cells (neutrophils) play an important role in the systemic inflammatory response syndrome and the development of sepsis. These cells are essential for the defense against microorganisms, but may also cause tissue damage. Therefore, neutrophil numbers and activity are considered to be tightly regulated. Previous studies have investigated gene transcription during experimental endotoxemia in whole blood and peripheral blood mononuclear cells. However, the gene transcription response of the circulating pool of neutrophils to systemic inflammatory stimulation in vivo is currently unclear. We examined neutrophil gene transcription kinetics in healthy human subjects (n=4) administered a single dose of endotoxin (LPS, 2 ng/kg iv). In addition, freshly isolated neutrophils were stimulated ex vivo with LPS, TNFα, G-CSF and GM-CSF to identify stimulus-specific gene transcription responses. Whole transcriptome microarray analysis of circulating neutrophils at 2, 4 and 6 hours after LPS infusion revealed activation of inflammatory networks which are involved in signaling of TNFα and IL-1α and IL-1β. The transcriptome profile of inflammatory activated neutrophils in vivo reflects extended survival and regulation of inflammatory responses. We show that these changes in neutrophil transcriptome are most likely due to a combination of early activation of circulating neutrophils by TNFα and G-CSF and a mobilization of young neutrophils from the bone marrow.
2012-06-05 | GSE35590 | GEO
Project description:Metabolic plasticity of tissues determines the degree and reversibility of organ damage under inflammatory challenges. While treating septic cardiomyopathy (SCM) with high mortality, metabolic management should be considered. Still, similar pan-organ metabolic anomalies usually yield contrasting results in each one, highlighting the necessity to identify cardiac-specific metabolic regulators. Nicotinamide adenine dinucleotide (NAD+) signaling is fundamental to cellular metabolic homeostasis and inflammatory response, and cardiomyocyte-enriched NAD+-consuming enzymes programming metabolism against sepsis and their roles in SCM remain undefined. In this study, we explored the expression patterns of NAD+-consuming enzymes of heart and found Mono-ADP-ribosyl hydrolase MacroD1 protein was distinctly enriched in rodent and AC16 human cardiomyocytes and upregulated during severe endotoxemia. Genetic and pharmacological inactivation of MacroD1 counteracted myocardial metabolic impairment, lipid accumulation, inflammatory infiltrate, cardiac dysfunction, and mortality risk induced by septic challenges in mice. Mechanistically, MacroD1 selectively modulated the activity of mitochondrial complex I (MCI), a proximal respiratory unit most vulnerable to early endotoxemia. Its inhibition enhanced MARylation of NDUFB9, an accessory assembly factor of MCI proton-pumping module ND5, and therefore binding to ND5 for preserving MCI activity in sepsis, restraining bioenergetic deficiency, oxidative stress-coupled NLRP3 inflammasome activation, and pyroptosis of cardiomyocytes. Our research reveals that MacroD1 dictates cardiac tolerance to sepsis by configuring MCI-coupled bioenergetic reserve and pyroptosis of cardiomyocytes. Blockade of MacroD1 promises specific prevention of SCM.
2025-06-18 | GSE253829 | GEO
Project description:Endotoxemia is a key feature of sepsis pathogenesis and has also been found to mediate the pathophysiology of multiple chronic inflammatory conditions. In this work, we expand upon a model of endotoxemia due to lipopolysaccharide (LPS) using zebrafish and demonstrate that this model displays activation of inflammatory and pro-coagulant genes, impaired coagulation in response to endothelial injury, and signs of organ dysfunction. An in silico analysis revealed that there were multiple associations between the RNA-seq signature of LPS treated embryos and the RNA-seq signature of genes and drugs involving diverse pathways. An in vivo screen involving >1,500 FDA approved drugs identified multiple compounds spanning several drug categories that partially or completely prevented endotoxemic death. Three small molecules including one anticoagulant dabigatran were identified through both the in vivo and in silico analyses. Dabigatran, a direct thrombin inhibitor, significantly reduced the upregulation of inflammatory cytokines and pro-coagulant genes and completely protected zebrafish from endotoxemic death due to LPS. However, other anticoagulants argatroban (direct thrombin inhibitor), and rivaroxaban and apixaban, (factor Xa inhibitors), conferred no such protection. Lastly, prothrombin mutant fish displayed no increase in survival when treated with LPS. These data together suggest that dabigatran protects zebrafish from endotoxemia through a mechanism independent of its anticoagulant effect. In summary, our in silico and in vivo analyses reveals that dabigatran and several other novel small molecules prevent LPS induced endotoxemia and warrant further therapeutic exploration in inflammatory conditions, both acute and chronic.
2025-10-03 | GSE245299 | GEO
Project description:Acute Respiratory Distress Syndrome (ARDS) is a very common clinical entity and a major cause of morbidity and mortality in the critical care setting. Historically, ARDS has been associated with mortality ranging from 40% to 60% . In the US alone,200,000 new cases of ARDS occur every year. ARDS can be associated with different clinical disorders affecting the lungs. A novel ex-vivo swine model developed by our group permits measurements of lung pathophysiology and simultaneous collection of lung and liver tissue for histologic and molecular comparisons during the early phase of the response to endotoxemia. In this preparation, endotoxemia causes a liver-dependent inflammatory response and severe lung injury and dysfunction. We chose swine, as an experimental animal because, like humans, they are especially sensitive to endotoxin and the pathophysiology of the response appears to be similar to that in humans. Gene expression was evaluated in swine liver before and after endotoxin treatment.
2013-01-10 | E-MTAB-1436 | biostudies-arrayexpress