Effect of GSDMD knockout on hyperoxia-induced lung and retinal injury
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE206087 | GEO | 2023/01/11
REPOSITORIES: GEO
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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:Gasdermin D (GSDMD) is the executioner of pyroptosis, which is important for host defense against pathogen infection. After activation, caspase-mediated cleavage of GSDMD liberates an N-terminal fragment (GSDMD-NT), which oligomerizes and forms pores in the plasma membrane, leading to cell death and subsequent release of proinflammatory cytokines. How this process is spatiotemporally controlled to promote pyroptosis in cells has been a fundamental, unaddressed question. Here, we identify GSDMD as a substrate for reversible S-palmitoylation on cysteine 192 (Cys192) in response to lipopolysaccharide (LPS) stimulation. We found that the palmitoyl acyltransferase DHHC7palmitoylates GSDMD to direct its cleavage by caspases in pyroptosis by promoting the interaction of GSDMD and caspases. We further show that after GSDMD cleavage, palmitoylation of GSDMD-NTpromotes its plasma membrane translocation and binding, and then acyl protein thioesterase 2 (APT2) depalmitoylates GSDMD-NT to unmask the Cys192 residue to promote oxidation-mediated oligomerization and pyroptosis. Perturbation of either palmitoylation or depalmitoylation suppresses pyroptosis, extends the survival of mice from LPS-induced lethal septic shock and sensitizes mice to bacterial infection. Thus. our findings reveal a model through which a palmitoylation-depalmitoylationrelay spatially and temporally controls GSDMD activation in pyroptosis.
2024-02-25 | GSE252911 | GEO
Project description:Gasdermin D (GSDMD) is the executioner of pyroptosis, which is important for host defense against pathogen infection. After activation, caspase-mediated cleavage of GSDMD liberates an N-terminal fragment (GSDMD-NT), which oligomerizes and forms pores in the plasma membrane, leading to cell death and subsequent release of proinflammatory cytokines. How this process is spatiotemporally controlled to promote pyroptosis in cells has been a fundamental, unaddressed question. Here, we identify GSDMD as a substrate for reversible S-palmitoylation on cysteine 192 (Cys192) in response to lipopolysaccharide (LPS) stimulation. We found that the palmitoyl acyltransferase DHHC7palmitoylates GSDMD to direct its cleavage by caspases in pyroptosis by promoting the interaction of GSDMD and caspases. We further show that after GSDMD cleavage, palmitoylation of GSDMD-NTpromotes its plasma membrane translocation and binding, and then acyl protein thioesterase 2 (APT2) depalmitoylates GSDMD-NT to unmask the Cys192 residue to promote oxidation-mediated oligomerization and pyroptosis. Perturbation of either palmitoylation or depalmitoylation suppresses pyroptosis, extends the survival of mice from LPS-induced lethal septic shock and sensitizes mice to bacterial infection. Thus. our findings reveal a model through which a palmitoylation-depalmitoylationrelay spatially and temporally controls GSDMD activation in pyroptosis.
2024-02-25 | GSE252893 | GEO
Project description:We performed miRNA array analysis from 2 groups (neonatal lung control, neonatal lung after hyperoxia). We used pools of every 100ng of total RNA of three samples for each groups.
2021-04-06 | GSE129406 | GEO
Project description:It is unclear why preterm birth increases risk of cardiovascular disease later in life. Studies in mice indicate excess oxygen typically used to treat preterm infants causes pulmonary hypertension, cardiac failure, and shortens lifespan. We previously reported neonatal hyperoxia causes pulmonary hypertension in aged mice as defined pathologically by pulmonary capillary rarefaction, dilation of pulmonary arterioles and veins, right ventricular hypertrophy, and reduced lifespan. These changes were preceded by a pronounced growth inhibition of cardiomyocytes lining the pulmonary vein and extending into the left atria, resulting in diastolic heart failure as the mice aged. To identify transcriptional changes by which hyperoxia suppresses proliferation of these cardiomyocytes, newborn mice were exposed to room air or 100% oxygen between birth and postnatal day 4. RNA was then isolated from atria of 3 room air and 4 hyperoxia-exposed mice and used to probe Affymetrix mouse array 430 versus 2.0
2021-02-23 | E-MTAB-9008 | biostudies-arrayexpress
Project description:The NLRP3 inflammasome and IL-1β are essential for scleroderma pathogenesis. Nevertheless, the role of pyroptosis executor gasdermin D(GSDMD), which is a downstream molecule of NLRP3 and is required for IL-1β release in some situations, has not yet been well elucidated in scleroderma. The purpose of this study was to explore the differences in the degree of skin fibrosis between GSDMD-/- and wild type mice in a bleomycin-induced scleroderma model, and the molecular pathways that may be involved.Total RNA from skin biopsies from GSDMD-/- and wild type mice after subcutaneous injection of BLM to induce skin fibrosis was examined by nextGen RNA sequencing
2022-02-16 | GSE196637 | 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:Purpose: In the C57BL/6J mouse retina, hyperoxia-induced degeneration of photoreceptors shows strong regional variation, beginning at a locus ~0.5mm inferior to the optic disc. To identify gene expression differences that might underlie this variability in vulnerability, we have used microarray techniques to describe regional (superior-inferior) variations in gene expression in the retina. Methods: Young adult C57BL/6J mice raised in dim cyclic illumination (12h 5lux, 12h darkness) were exposed to hyperoxia (75% oxygen for 2w). Retinas were collected from hyperoxia-exposed and control animals without fixation, and divided into superior and inferior halves. RNA was extracted from each sample, purified and hybridised to mouse 1.0 ST arrays (Affymetrix). The consistency of the microarray results was assessed with quantitative PCR for selected genes. Expression data were analysed to identify genes and ncRNAs whose differential expression between superior and inferior retina could be associated with relative vulnerability to hyperoxia.
2010-04-08 | E-GEOD-21246 | biostudies-arrayexpress
Project description:This study is to examine the transcriptome of mononuclear cell populations in the neonatal lung. We investigated how acute hyperoxia-induced lung injury changes gene expression within these mononuclear populations: dendritic cells, interstitial monocytes/macrophages, and alveolar macrophages.
2022-02-28 | GSE127463 | GEO
Project description:Neonatal mouse exposed to hyperoxia
| PRJNA531182 | ENA