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| 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
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| 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.
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| 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.
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| Contributor(s) |
Cloonan S, Glass K |
| Citation(s) |
26752519 |
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| Submission date |
Apr 24, 2014 |
| Last update date |
Apr 01, 2016 |
| Contact name |
Augustine MK Choi |
| Organization name |
Weill Cornell Medical College
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| Department |
Department of Medicine
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| Street address |
525 East 68th Street, Room M-522, Box 130
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL17777 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [CDF: mogene10st_Mm_ENTREZG_17.1.0] |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA245321 |
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