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Series GSE166399 Query DataSets for GSE166399
Status Public on Sep 29, 2021
Title Effect of tumor necrosis factor receptor (Tnfr) deletion in ozone-induced pulmonary transcriptome changes in mice
Organism Mus musculus
Experiment type Expression profiling by array
Summary Background: Ozone (O3) is the predominant oxidant air pollutant associated with respiratory inflammation, lung dysfunction, and worsening preexisting airway diseases. We determined that TNFR signlaing pathway plays a key role in lung injury and inflammation caused by O3 in mice. However, downstream molecular mechanisms underlying TNFR pathway have not been investigated.
Methods: To investigate the role of TNFR pathway in gene expression changes, Tnfr1/2-deficient (Tnfr-/-) and wild-type (Tnfr+/+, C57BL/6J) mice were exposed to air or 0.3-ppm O3. Total RNAs were isolated from lung homogenates and cDNA microarray analyses were performed to elucidate TNFR-directed transcriptomics in basal lungs (air-exposed) as well as in the lung exposed to time course of O3 (24, 48, and 72 hr).
Results: O3 caused time-dependent changes in lung gene expressions with the greatest transcriptome changes at 48-72 hr of exposure in Tnfr+/+ mice. At early time of exposure (24 hr), acute phase and inflammatory responses gene as well as redox and lipid metabolism genes were increased by O3 while cell cycle and DNA damage repair genes were markedly increased by O3 at later time points (48-72 hr). Compared to Tnfr+/+ mice, Tnfr-/- mice had lowered expression of inflammatory response and vascular disorder-related genes at baseline (air). After O3 exposure, Tnfr-/- had enhanced expression of immune and inflammatory genes at 24 hr, indicating compensatory or adpative poentiation of immunity in Tnfr-/- mice. At 48 hr of O3 exposure, Tnfr-/- mice showed suppressed expression of genes involved in epithelial proliferation, inflammatory cell influxes and epithelial injury, compared to Tnfr+/+ mice. At 72 hr of O3 exposure, neurodegeneration and neurotransmitter transport genes were suppressed in Tnfr-/- than in Tnfr+/+.
Conclusion: Overall, deficiency of TNFR-mediated signaling in mouse lungs altered transcriptomes to protect lungs from O3-induced inflammation, cell proliferation, oxidative stress, and neuronal disorders.
 
Overall design PARALLEL study design with 24 samples comparing 8 groups of gene and exposure: (4 groups Tnfr+/+ wild type; air-24 hr O3-48 hr O3-72 hr O3 exposure) (4 groups Tnfr knockout; air-24 hr O3-48 hr O3-72 hr O3 exposure). Biological replicates: 3 per group.
 
Contributor(s) Kleeberger S, Cho H
Citation(s) 34573120
https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10091489
Submission date Feb 08, 2021
Last update date Oct 06, 2021
Contact name NIEHS Microarray Core
E-mail(s) microarray@niehs.nih.gov, liuliw@niehs.nih.gov
Organization name NIEHS
Department DIR
Lab Microarray Core
Street address 111 T.W. Alexander Drive
City RTP
State/province NC
ZIP/Postal code 27709
Country USA
 
Platforms (1)
GPL339 [MOE430A] Affymetrix Mouse Expression 430A Array
Samples (24)
GSM5071387 WT-Air Replicate 1
GSM5071388 WT-Air Replicate 2
GSM5071389 WT-Air Replicate 3
Relations
BioProject PRJNA700998

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE166399_RAW.tar 52.6 Mb (http)(custom) TAR (of CEL, CHP)
Processed data included within Sample table
Processed data provided as supplementary file

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