Aurothioglucose Enhances Pro-Angiogenic Pathway Activation in Lungs from Room Air and Hyperoxia-exposed Newborn Mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE145912 | GEO | 2020/07/15
REPOSITORIES: GEO
Similar Datasets
Project description:Aurothioglucose Enhances Pro-Angiogenic Pathway Activation in Lungs from Room Air and Hyperoxia-exposed Newborn Mice
| PRJNA608719 | ENA
Project description:Bronchopulmonary dysplasia (BPD), a long-term respiratory morbidity of prematurity, is characterized by attenuated alveolar and vascular development. Supplemental oxygen and immature antioxidant defenses contribute to BPD development. Our group identified thioredoxin reductase-1 (TXNRD1) as a therapeutic target to prevent BPD. The present studies evaluated the impact of the TXNRD1 inhibitor aurothioglucose (ATG) on pulmonary responses and gene expression in newborn C57BL/6 pups treated with saline or ATG (25 mg/kg ip) within 12 h of birth and exposed to room air (21% O2) or hyperoxia (>95% O2) for 72 h. Purified RNA from lung tissues was sequenced, and differential expression was evaluated. Hyperoxic exposure altered ~2,000 genes, including pathways involved in glutathione metabolism, intrinsic apoptosis signaling, and cell cycle regulation. The isolated effect of ATG treatment was limited primarily to genes that regulate angiogenesis and vascularization. In separate studies, pups were treated as described above and returned to room air until 14 days. Vascular density analyses were performed, and ANOVA indicated an independent effect of hyperoxia on vascular density and alveolar architecture at 14 days. Consistent with RNA-seq analyses, ATG significantly increased vascular density in room air, but not in hyperoxia-exposed pups. These findings provide insights into the mechanisms by which TXNRD1 inhibitors may enhance lung development.
| S-EPMC7347274 | biostudies-literature
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:This experiment aimed to investigate the differences in the transcriptional profile of the neurogenic niche regions of mouse pups that were raised in room air verses mouse pups that were exposed to hyperoxia during the neonatal period. Pups were housed in room air or hyperoxia (85% O2) from P0 to P14. Brain tissue (the subventricular zone and the hippocampus) was collected at P14 and 12 months of age. RNA was extracted from the brain tissue and the microarray labelling, hybridization, and scanning was conducted by the Génome Québec Innovation Centre (Montréal, Canada).
2023-01-03 | E-MTAB-11332 | biostudies-arrayexpress
Project description:To detect sex-specific differences in gene expression in a model of hyperoxic lung injury in adult C56BL/6J mice. In this dataset, we include the expression data obtained from lungs from 8-10 week old male and female WT C57BL/6J mice exposed to hyperoxia for 48 hours amd room air controls.These data were used to determine differences in transcriptome between male and female mice after hyperoxia exposure
2014-12-10 | GSE51039 | GEO
Project description:To detect sex-specific differences in gene expression in a model of hyperoxic lung injury in adult C56BL/6J mice. In this dataset, we include the expression data obtained from lungs from 8-10 week old male and female WT C57BL/6J mice exposed to hyperoxia for 48 hours amd room air controls.These data were used to determine differences in transcriptome between male and female mice after hyperoxia exposure 12 total samples were analyzed. We generated the following pairwise comparisons: 5 comparisons (M/F: male/female, A/O: air/oxygen): 1) M_O - M_A,
2) F_O - F_A,
3) M_O - F_O,
4) M_A - F_A,
5) (M_O - M_A) - (F_O - F_A). Genes with an FDR≤5% and a fold-change ≥1.4 were selected.
2014-12-10 | E-GEOD-51039 | biostudies-arrayexpress
Project description:Extremely preterm infants are often treated with supraphysiological oxygen which contributes to the development of bronchopulmonary dysplasia (BPD). These same infants exhibit compromised antioxidant capacities due in part to selenium (Se) deficiency. The present study was designed to develop a perinatal Se deficiency mouse model, identify the effects of newborn hyperoxia exposure, and explore alternative pathways affected by Se deficiency (SeD) that would contribute to impaired lung development. Se deficient breeding pairs were generated, once pups were born, they were exposed to room air or 85% O2 for 14 d. Survival, antioxidant and Nrf2-regulated protein expression, and RNA seq analyses were performed. Greater than 40% mortality was observed in Se deficient (SeD), hyperoxia exposed pups. Surviving SeD pups had greater lung growth deficits than Se sufficient (SeS) pups exposed to hyperoxia. Gpx2 and 4 protein and Gpx activity were significantly decreased in SeD pups. Nrf2-regulated proteins, NQO1 and Gclc were increased in the setting of Se deficiency and hyperoxia exposure. RNA seq revealed significant decreases in the Wnt/-catenin and Notch pathways. Se is a biologically relevant modulator of perinatal lung development and antioxidant responses, especially in the context of hyperoxia exposure. RNA seq implicates pathways essential for normal lung development are dysregulated by Se deficiency.
2024-05-01 | GSE255744 | 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:Preterm newborns that receive oxygen therapy often develop bronchopulmonary dysplasia (BPD), which is abnormal lung development characterized by impaired alveologenesis. Oxygen-mediated injury is thought to disrupt normal lung growth and development. However, the mechanism of hyperoxia-induced BPD has not been extensively investigated. We established a neonatal mouse model to investigate the effects of normobaric hyperoxia on retinoid metabolism and retinoid receptor expression.Newborn mice were exposed to hyperoxic or normoxic conditions for 15 days. The concentration of retinol and retinyl palmitate in the lung was measured by HPLC to gauge retinoid metabolism. Retinoid receptor mRNA levels were assessed by real-time PCR. Proliferation and retinoid receptor expression in A549 cells were assessed in the presence and absence of exogenous vitamin A.Hyperoxia significantly reduced the body and lung weight of neonatal mice. Hyperoxia also downregulated expression of RARα, RARγ, and RXRγ in the lungs of neonatal mice. In vitro, hyperoxia inhibited proliferation and expression of retinoid receptors in A549 cells.Hyperoxia disrupted retinoid receptor expression in neonatal mice.
| S-EPMC4624932 | biostudies-literature
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.
2010-08-06 | GSE23437 | GEO