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Series GSE29632 Query DataSets for GSE29632
Status Public on May 25, 2012
Title Effect of Nrf2 deletion in postnatal lung development and BPD phenotype in newborn mice
Organism Mus musculus
Experiment type Expression profiling by array
Summary Background: Nrf2 is an essential cytoprotective transcription factor. However, association of Nrf2 in organ development and neonatal disease is rarely examined. Hyperoxia exposure to newborn rodents generates pulmonary phenotypes which resemble bronchopulmonary dysplasia (BPD) of prematurity.
Methods: To investigate the role of Nrf2 in lung maturation and BPD pathogenesis, Nrf2-deficient (Nrf2-/-) and wild-type (Nrf2+/+) neonates were exposed to air or hyperoxia (O2). Transcriptome analysis determined Nrf2-directed mechanisms in premature lung. Lung injury was assessed by bronchoalveolar lavage analysis and histopathology.
Results: In Nrf2-/- neonates, basal expression of cell cycle machinery, redox balance, and lipid/carbohydrate metabolism genes were suppressed while immunity genes were overexpressed compared to Nrf2+/+ pups. O2-induced mortality and pulmonary inflammation/injury were significantly higher in Nrf2-/- than in Nrf2+/+. Lung DNA lesion and oxidation were greater in Nrf2-/- than in Nrf2+/+, constitutively and after O2. Nrf2-dependent genes modulated cellular growth/proliferation, defense, immunity, and lipid metabolism against hyperoxia. Bioinformatic elucidation of Nrf2 binding motifs and augmented O2-induced inflammation in genetically deficient neonates validated Gpx2 and Marco as Nrf2 effectors.
Conclusion: Overall, Nrf2 in underdeveloped lungs orchestrated cell cycle, morphogenesis, and immunity as well as cellular defense constitutively and under oxidant stress. Results provide putative molecular mechanisms of Nrf2-directed lung alveolarization and BPD of prematurity.
Overall design PARALLEL study design with 42 samples comparing 14 groups of age (P1 to P4 corresponding to day 0 to day 3 animals), gene, and exposure: (4 groups Nrf+/+ wild type P1-P4 air exposure) (4 groups Nrf -/- knockout P1-P4 air exposure), (3 groups Nrf+/+ wild type P2-P4 with 100 percent O2 (hyperoxia exposure) and 3 groupsNrf -/- knockout P2-P4 with 100 percent O2 (hyperoxia exposure)) Biological replicates: 3 per group
Contributor(s) Kleeberger S, Cho H
Citation(s) 22400915
Submission date May 31, 2011
Last update date Feb 11, 2019
Contact name Steven R Kleeberger
Organization name National Institute of Environmental Health Sciences, NIH
Lab Laboratory of Respiratory Biology
Street address 111 TW Alexander Dr., Building 101, MD D-201
City Research Triangle Park
State/province NC
ZIP/Postal code 27709
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (42)
GSM734358 Wild type postnatal day 1 (P1, birthday) replicate 1
GSM734359 Wild type postnatal day 1 (P1, birthday) replicate 2
GSM734360 Wild type postnatal day 1 (P1, birthday) replicate 3
BioProject PRJNA141263

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE29632_RAW.tar 165.0 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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