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Series GSE57048 Query DataSets for GSE57048
Status Public on Jan 01, 2016
Title Irp2 mediates cigarette smoke-induced bronchitis and emphysema via regulation of cytochrome c oxidase and mitochondrial iron loading.
Organism Mus musculus
Experiment type Expression profiling by array
Summary Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death globally, is influenced by both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as a candidate COPD susceptibility gene based on genetic association studies, with IRP2 increased in the lungs of COPD patients. Here we demonstrate that mice deficient in IRP2 are protected from cigarette smoke (CS)-induced COPD. Using RIP-Seq, RNA-Seq, gene expression and pathway analysis, we identify IRP2 as a regulator of mitochondrial function in the lung. We show that an increase in IRP2 results in a cytochrome c oxidase (COX)-dependent alteration in oxidative capacity and mitochondrial-iron dysfunction involving frataxin. We demonstrate that mice with impaired COX or frataxin activity have altered responses to CS and show that overexpressing IRP2 in vivo alters mitochondrial dynamics. These data suggest a critical role of the mitochondria-iron axis in mediating the pathogenesis of COPD.
We used microarrays to compare the global programme of gene expression in the lungs of WT mice compared ot the lungs harvested from Irp2-/- mice.
Overall design n=6 Wildtype C57/BL6 mice (n=3 males, 3 females), n=5 (n=2 males, n =3 females) Irp2-/- C57/BL6 mice, approx 28-32 weeks were sacrificied, lungs removed and snap forzen. RNA isolated after one freeze thaw cycle using the Qiagen RNeasy Kit.
Contributor(s) Cloonan S, Glass K
Citation(s) 26752519
Submission date Apr 24, 2014
Last update date Apr 01, 2016
Contact name Augustine MK Choi
Organization name Weill Cornell Medical College
Department Department of Medicine
Street address 525 East 68th Street, Room M-522, Box 130
City New York
State/province NY
ZIP/Postal code 10065
Country USA
Platforms (1)
GPL17777 [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [CDF: mogene10st_Mm_ENTREZG_17.1.0]
Samples (11)
GSM1373723 IREB2 knock-out Male 1
GSM1373724 IREB2 knock-out Male 2
GSM1373725 IREB2 knock-out Female 1
BioProject PRJNA245321

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE57048_RAW.tar 76.1 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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