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Series GSE57073 Query DataSets for GSE57073
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 Homo sapiens
Experiment type Expression profiling by high throughput sequencing
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.
Overall design 1.5 X106 Beas2B cells (purchased from ATCC) with or without 10 μM DFO (16 h) (15 cm2 dishes) were washed with ice cold PBS and collected into 2 ml eppendorfs by scraping. RNA immunoprecipitation was carried out using the Magna RIP™ RNA-Binding Protein Immunoprecipitation Kit (Millipore, Billerica, MA). 4 μg of Irp2 (7H6: sc-33682, Santa Cruz, Dallas, Texas) or 4 μg of IgG rabbit control antibody (sc-2749, Santa Cruz) were added to supernatants and incubated overnight at 4°C. RNA was extracted from Magna RIP™ beads by Trizol extraction. Samples were prepared for RNA-Seq using the TruSeq RNA-Seq Lib Prep Reagent (Illumina, San Diego, CA) and performed on the Illumina HiSeq2000 platform.
Contributor(s) Cloonan S, Glass K
Citation(s) 26752519
Submission date Apr 25, 2014
Last update date May 15, 2019
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)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (6)
GSM1374091 IRP2 immunoprecipitation from untreated cells, replicate 1
GSM1374092 IRP2 immunoprecipitation from untreated cells, replicate 2
GSM1374093 Immunoprecipitation with IGG antibody from untreated cells
BioProject PRJNA245391
SRA SRP041444

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

Supplementary file Size Download File type/resource
GSE57073_CTRL12vsDFO12_Peaks_LowFilter.txt.gz 623.8 Kb (ftp)(http) TXT
GSE57073_CTRL_Both.txt_Annotated.txt.gz 1.5 Mb (ftp)(http) TXT
GSE57073_DFO12vsCTRL12_Peaks_LowFilter.txt.gz 170.6 Kb (ftp)(http) TXT
GSE57073_DFO_Both.txt_Annotated.txt.gz 473.9 Kb (ftp)(http) TXT
GSE57073_IREB_Both.txt_Annotated.txt.gz 430.5 Kb (ftp)(http) TXT
GSE57073_SC1_CONTROL_12_Peaks_LowFilter.txt.gz 584.5 Kb (ftp)(http) TXT
GSE57073_SC2_DFO_12_Peaks_LowFilter.txt.gz 306.1 Kb (ftp)(http) TXT
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Raw data are available in SRA

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