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| Status |
Public on Feb 18, 2017 |
| Title |
MMP28 is a key contributor to emphysema pathogenesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Chronic Obstructive Pulmonary Disease, which is comprised of chronic bronchitis and emphysema, is a leading cause of morbidity and mortality. Because tissue destruction is the prominent characteristic of emphysema, extracellular proteinases, particularly those with elastolytic ability, are often considered to be key drivers in this disease. Several human and mouse studies have implicated roles for matrix metalloproteinases (MMPs), particularly macrophage-derived proteinases, in COPD pathogenesis. MMP28 is expressed by the pulmonary epithelium and macrophage, and we have found that it regulates macrophage recruitment and polarization. We hypothesized that MMP28 would have contributory roles in emphysema via alteration of macrophage numbers and activation. Because of the established association of emphysema pathogenesis to macrophage influx, we evaluated the inflammatory changes and lung histology of Mmp28-/- mice exposed to 3 and 6 months of cigarette smoke. At earlier time-points, we found altered macrophage polarization in the smoke-exposed Mmp28-/- lung consistent with other published findings that MMP28 regulates macrophage activation. At both 3 and 6 months, Mmp28-/- mice had blunted inflammatory responses more closely resembling non-smoked mice, with a reduction in neutrophil recruitment and CXCL1 chemokine expression. By 6 months, Mmp28-/- mice were protected from emphysema. These results highlight a previously unrecognized role for MMP28 in promoting chronic lung inflammation and tissue remodeling induced by cigarette smoke and highlight another potential target to modulate COPD.
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| Overall design |
Total RNA from whole lungs homogenates of wildtype and knockout (Mmp28-/-) mice exposed to room air or 3 months of cigarette smoke was isolated and hybidized to Illumina Mouse Ref-8 v2 Expression BeadChips.
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| Contributor(s) |
Gharib SA |
| Citation(s) |
28399390 |
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| Submission date |
Jan 21, 2017 |
| Last update date |
Oct 19, 2022 |
| Contact name |
Sina Gharib |
| E-mail(s) |
sagharib@uw.edu
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| Organization name |
University of Washington
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| Department |
Medicine
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| Street address |
850 Republican St.
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (16)
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| GSM2464602 |
wild type exposed to cigarette smoke replicate 1 |
| GSM2464603 |
wild type exposed to cigarette smoke replicate 2 |
| GSM2464604 |
wild type exposed to cigarette smoke replicate 3 |
| GSM2464605 |
wild type exposed to cigarette smoke replicate 4 |
| GSM2464606 |
wild type exposed to cigarette smoke replicate 5 |
| GSM2464607 |
knock out exposed to cigarette smoke replicate 1 |
| GSM2464608 |
knock out exposed to cigarette smoke replicate 2 |
| GSM2464609 |
knock out exposed to cigarette smoke replicate 3 |
| GSM2464610 |
knock out exposed to cigarette smoke replicate 4 |
| GSM2464611 |
knock out exposed to cigarette smoke replicate 5 |
| GSM2464612 |
wild type exposed to room air replicate 1 |
| GSM2464613 |
wild type exposed to room air replicate 2 |
| GSM2464614 |
wild type exposed to room air replicate 3 |
| GSM2464615 |
knock out exposed to room air replicate 1 |
| GSM2464616 |
knock out exposed to room air replicate 2 |
| GSM2464617 |
knock out exposed to room air replicate 3 |
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| Relations |
| BioProject |
PRJNA362783 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE93898_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
| GSE93898_non-normalized.txt.gz |
2.4 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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