Effect of GSDMD knockout on hyperoxia-induced lung and retinal injury
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ABSTRACT:
PROVIDER: PRJNA849166 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR19649533.fastq.gz | Fastqsanger.gz | |||
| SRR19649534.fastq.gz | Fastqsanger.gz | |||
| SRR19649535.fastq.gz | Fastqsanger.gz | |||
| SRR19649536.fastq.gz | Fastqsanger.gz | |||
| SRR19649537.fastq.gz | Fastqsanger.gz |
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Project description:To investigate the role of GSDMD-mediated pyroptosis in neonatal lung and retinal injury induced by hyperoxia We performed RNA-seq of lung and retina of newborn rats exposed to hyperoxia for 2 weeks
2023-01-11 | GSE206087 | GEO
Project description:GSDMD knockout alleviates hyperoxia-induced hippocampal brain injury in neonatal mice
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Project description:Exposure to neonatal hyperoxia is associated with brain injury and poor neurodevelopmental outcomes in preterm infants. Our goal was to determine the pathogenic role of GDMD in hiipocampal in injury in newborn mice
2023-09-13 | GSE241549 | GEO
Project description:Premature infants require oxygen supplementation to survive, but excess oxygen causes retinovascular growth suppression that underlies the leading cause of infant blindness known as retinopathy of prematurity (ROP). We analyzed changes in intermediary metabolism during hyperoxia in human retinal endothelial cells (RECs) and human retinal Müller glia, which coexist through glutamine consumption and production, respectively. Using a stable isotope labeling technique in human RECs and human Müller cells in culture, here we show that Müller cells in hyperoxia block entry of glycolytic carbon into the tricarboxylic acid (TCA) cycle and instead oxidize glutamine. In hyperoxia, catabolism of glutamine increased ammonium release by 2-fold. Hyperoxia induces glutamine-fueled anaplerosis that reverses basal Müller cell metabolism from production to consumption of glutamine.
2020-03-12 | MTBLS1228 | MetaboLights
Project description:BackgroundNeonatal hyperoxia exposure is associated with brain injury and poor neurodevelopment outcomes in preterm infants. Our previous studies in neonatal rodent models have shown that hyperoxia stimulates the brain's inflammasome pathway, leading to the activation of gasdermin D (GSDMD), a key executor of pyroptotic inflammatory cell death. Moreover, we found pharmacological inhibition of caspase-1, which blocks GSDMD activation, attenuates hyperoxia-induced brain injury in neonatal mice. We hypothesized that GSDMD plays a pathogenic role in hyperoxia-induced neonatal brain injury and that GSDMD gene knockout (KO) will alleviate hyperoxia-induced brain injury.MethodsNewborn GSDMD knockout mice and their wildtype (WT) littermates were randomized within 24 h after birth to be exposed to room air or hyperoxia (85% O2) from postnatal days 1 to 14. Hippocampal brain inflammatory injury was assessed in brain sections by immunohistology for allograft inflammatory factor 1 (AIF1) and CD68, markers of microglial activation. Cell proliferation was evaluated by Ki-67 staining, and cell death was determined by TUNEL assay. RNA sequencing of the hippocampus was performed to identify the transcriptional effects of hyperoxia and GSDMD-KO, and qRT-PCR was performed to confirm some of the significantly regulated genes.ResultsHyperoxia-exposed WT mice had increased microglia consistent with activation, which was associated with decreased cell proliferation and increased cell death in the hippocampal area. Conversely, hyperoxia-exposed GSDMD-KO mice exhibited considerable resistance to hyperoxia as O2 exposure did not increase AIF1 + , CD68 + , or TUNEL + cell numbers or decrease cell proliferation. Hyperoxia exposure differentially regulated 258 genes in WT and only 16 in GSDMD-KO mice compared to room air-exposed WT and GSDMD-KO, respectively. Gene set enrichment analysis showed that in the WT brain, hyperoxia differentially regulated genes associated with neuronal and vascular development and differentiation, axonogenesis, glial cell differentiation, hypoxia-induced factor 1 pathway, and neuronal growth factor pathways. These changes were prevented by GSDMD-KO.ConclusionsGSDMD-KO alleviates hyperoxia-induced inflammatory injury, cell survival and death, and alterations of transcriptional gene expression of pathways involved in neuronal growth, development, and differentiation in the hippocampus of neonatal mice. This suggests that GSDMD plays a pathogenic role in preterm brain injury, and targeting GSDMD may be beneficial in preventing and treating brain injury and poor neurodevelopmental outcomes in preterm infants.
| S-EPMC10486051 | biostudies-literature
Project description:Acute kidney injury(AKI) is associated with an increased risk of chronic kidney disease(CKD). There is still a lack of effective prevention for AKI-CKD transition. In the present study, we simultaneously explored the contribution of GSDMD and GSDME in folic acid (FA)-induced nephropathy, a model mimicking the essential components of the AKI-CKD transition. We found that blockage of both GSDMD and GSDME-mediated pyroptosis could have accumulative protection against FA-induced AKI-CKD transition. GSDME-mediated pyroptosis played a crucial role in tubular cell damage. GSDMD could exert important functions in infiltration of inflammatory cells and NETs formation. Pyroptotic tubular cells triggered NETs generation and macrophage polarization. NETs promoted macrophage-to-myofibroblast transition. Our results illustrated the orchestration of GSDMD and GSDME in AKI-CKD transition, providing new insights into the molecular mechanism for the clinical dilemma.
2024-10-31 | GSE245446 | GEO
Project description:Protective roles of Nrf2, a key transcription factor for antioxidant and defense genes, have been determined in oxidative lung injury, and health benefits of Nrf2 agonists including sulforaphane have been demonstrated. The current study was designed to investigate the effect of sulforaphane on model acute lung injury and sulforaphane-mediated transcriptome changes in mouse lungs. Adult mice genetically deficient in Nrf2 (Nrf2-/-) and wild-type controls (Nrf2+/+, ICR) received oral sulforaphane (9 mmol/daily) or vehicle before (-5, -3, -1 days) hyperoxia or air exposure (3 days), and lung injury and gene expression changes were assessed. Sulforaphane significantly reduced hyperoxia-induced airway injury, inflammation, and mucus hypersecretion in Nrf2+/+ mice while relatively marginal treatment effect was found in Nrf2-/- mice. Sulforaphane significantly altered expression of lung genes associated with oxidative phosphorylation and mitochondrial dysfunction (Atp2a2, Cox7a1, Ndufa1) basally and cell function/cycle and protein metabolism (Actr1a, Wasf2, Ccne1, Gtpbp4) after hyperoxia in Nrf2+/+ mice. Nrf2-dependently modulated lung genes by sulforaphane and hyperoxia were associated with tissue development and hereditary disorders (Slc25a3, Pccb, Psmc3ip). Results demonstrate preventive roles of sulforaphane against oxidant lung injury in mice, and reveal potential downstream mechanisms. Our observations also suggest Nrf2-independent mechanisms of sulforaphane in prevention of acute lung injury.
2015-06-01 | GSE58654 | GEO
Project description:PURPOSE: Hyperoxia is toxic to photoreceptors, and this toxicity may be important in the progress of retinal dystrophies. This microarray study examines gene expression induced in the C57BL/6J mouse retina by hyperoxia over the 14-day period during which photoreceptors first resist, then succumb to, hyperoxia. METHODS: Young adult C57BL/6J mice were exposed to hyperoxia (75% oxygen) for up to 14 days. On day 0 (control), day 3, day 7, and day 14, retinal RNA was extracted and processed on Affymetrix GeneChip Mouse Genome 430 2.0 arrays. Microarray data were analyzed using GCOS Version 1.4 and GeneSpring Version 7.3.1. RESULTS: The overall numbers of hyperoxia-regulated genes increased monotonically with exposure. Within that increase, however, a distinctive temporal pattern was apparent. At 3 days exposure, there was prominent upregulation of genes associated with neuroprotection. By day 14, these early-responsive genes were downregulated, and genes related to cell death were strongly expressed. At day 7, the regulation of these genes was mixed, indicating a possible transition period from stability at day 3 to degeneration at day 14. CONCLUSIONS: Microarray analysis of the response of the retina to prolonged hyperoxia demonstrated a temporal pattern involving early neuroprotection and later cell death, and provided insight into the mechanisms involved in the two phases of response. As hyperoxia is a consistent feature of the late stages of photoreceptor degenerations, understanding the mechanisms of oxygen toxicity may be important therapeutically. 4 timepoints in total, 0d (control), 3d, 7d and 14d and a replicate per timepoint. Total of 8 chips.
2010-08-05 | E-GEOD-23437 | biostudies-arrayexpress
Project description:Oxygen therapy is essential for cure critically patients in ICU, but hyperoxia can cause damage to many organs, including the lungs, leading to Hyperoxia Acute Lung Injury (HALI), a mild type of acute respiratory distress syndrome (ARDS). However, the comprehensive pathogenesis and regulation mechanisms underlying the development of HALI remain unclear. In this study, we conducted a mouse model with hyperoxia treatment and sequenced the gene expression pattern of HALI-mice and relative control (RNA-seq).
2024-04-05 | GSE237260 | GEO
Project description:We have previously demonstrated that deletion of the Cebpa gene in the developing fetal mouse lung caused death soon after birth from the failure of lung maturation. Many of the transcriptional pathways regulating morphogenesis of the fetal lung are induced postnatally and mediate repair of the injured lung. We hypothesized that C/EBPa plays a role in protection of the alveolar epithelium following hyperoxia injury of the mature lung. Transgenic Cebpa∆/∆ mice in which Cebpa was conditionally deleted from Clara cells (from early gestation) and type II cells (from near-term) were developed. Cebpa∆/∆ mice grow normally without any pulmonary abnormalities. Cebpa∆/∆ mice were highly susceptible to hyperoxia. Cebpa∆/∆ mice died within 4d after hyperoxia associated with severe lung inflammation and altered surfactant components at a time when all control mice survived. Microarrays were analyzed on isolated type II cells at an early stage (24h) of hyperoxia exposure to detect the primary genes influenced by deletion of Cebpa. The associated network analysis revealed the reduced expression of key genes related to surfactant lipid and protein homeostasis, such as Srebf, Scap, Lpcat1, Abca3, Sftpb, and Napsa. Genes for the cell signaling, immune response, and protective antioxidants, including GSH and Vnn-1,3, were decreased in the Cebpa∆/∆ mice lung. C/EBPa did not play a critical role in postnatal pulmonary function under normal conditions. In contrast, in the absence of C/EBPa, exposure to hyperoxia caused respiratory failure, supporting the concept that C/EBPa plays an important role in enhancing epithelial cell survival, surfactant lipid homeostasis, and maturation of SP-B from pro-SP-B.
2009-12-01 | GSE14917 | GEO