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Status |
Public on Apr 23, 2024 |
Title |
Multi-tissue transcriptomic and metabolomic profile of ozone exposure in male WKY rats |
Organism |
Rattus norvegicus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Air pollutant exposures have been linked to systemic disease; however, underlying mechanisms between single-tissue exposures and systemic responses are poorly understood. A prototypic inducer of stress, ozone causes respiratory and systemic, multiorgan effects through neuroendocrine stress response activation. The goal of the presented study was to assess transcriptomic signatures of multiple tissues and serum metabolomics to understand how neuroendocrine and adrenal-derived stress hormones contribute to multiorgan health outcomes. Male Wistar Kyoto rats (12-13 weeks old) were exposed to filtered air or 0.8 ppm ozone for 4-hours, and blood/tissues were collected immediately post-exposure. Each tissue had distinct expression profile at baseline. Ozone changed (adjusted p-value < .1, absolute fold-change > 50%) 5,102 genes in muscle, 2,516 in adrenals, 1,640 in lung, 1,333 in liver, 1,242 in adrenals and 274 in hypothalamus. Serum metabolomic analysis identified 863 metabolites, of which 447 were significantly altered in ozone-exposed rats (adjusted p-value < .1, absolute fold change > 20%). Although overall hypoxia, GPCR signaling and glucocorticoid signaling pathways were commonly changed in most tissues, gene signatures within overrepresented pathways showed limited overlap between tissues. This pattern suggested the distribution of receptors and transcriptional mechanisms for stress hormones are likely tissue-specific and involve induction of different gene sets with shared initiating triggers. Metabolomic analysis suggested major changes in lipids, amino acids and metabolites linked to gut microbiome, which correlated with transcriptional changes identified through pathway analysis within liver, muscle, and adipose tissues. Systems-level examination of tissue-specific biological mechanisms could further understanding of air pollution-related health consequences.
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Overall design |
Examination of transcriptomic data from tissues (lung, hypothalamus, adrenals, liver, adipose, and muscle) from male WKY rats exposed to either air or 0.8ppm ozone for 4 hours
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Contributor(s) |
Jackson T, House J, Henriquez A, Schladweiler M, Jackson K, Fisher A, Snow S, Alewel D, Motsinger-Reif A, Kodavanti U |
Citation(s) |
37690105 |
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Submission date |
Jun 02, 2023 |
Last update date |
Apr 23, 2024 |
Contact name |
Thomas Jackson |
E-mail(s) |
jackson.thomas@epa.gov
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Phone |
9195414163
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Organization name |
United States Environmental Protection Agency
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Department |
CPHEA
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Street address |
109 TW Alexander Dr
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City |
Research Triangle Park |
State/province |
NC |
ZIP/Postal code |
27711 |
Country |
USA |
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Platforms (1) |
GPL20084 |
Illumina NextSeq 500 (Rattus norvegicus) |
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Samples (70)
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Relations |
BioProject |
PRJNA979230 |
Supplementary file |
Size |
Download |
File type/resource |
GSE234042_Processed_Adipose_Norm.csv.gz |
852.5 Kb |
(ftp)(http) |
CSV |
GSE234042_Processed_Adrenal_Norm.csv.gz |
912.1 Kb |
(ftp)(http) |
CSV |
GSE234042_Processed_HT_Norm.csv.gz |
1.0 Mb |
(ftp)(http) |
CSV |
GSE234042_Processed_Liver_Norm.csv.gz |
909.9 Kb |
(ftp)(http) |
CSV |
GSE234042_Processed_Lung_Norm.csv.gz |
1.0 Mb |
(ftp)(http) |
CSV |
GSE234042_Processed_Muscle_Norm.csv.gz |
853.1 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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