Integrating murine gene expression studies to understand obstructive lung disease due to chronic inhaled endotoxin.
Endotoxin is a near ubiquitous environmental exposure that that has been associated with both asthma and chronic obstructive pulmonary disease (COPD). These obstructive lung diseases have a complex pathophysiology, making them difficult to study comprehensively in the context of endotoxin. Genome-wi...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3652821?pdf=render |
| _version_ | 1819140471401742336 |
|---|---|
| author | Peggy S Lai Oliver Hofmann Rebecca M Baron Manuela Cernadas Quanxin Ryan Meng Herbert S Bresler David M Brass Ivana V Yang David A Schwartz David C Christiani Winston Hide |
| author_facet | Peggy S Lai Oliver Hofmann Rebecca M Baron Manuela Cernadas Quanxin Ryan Meng Herbert S Bresler David M Brass Ivana V Yang David A Schwartz David C Christiani Winston Hide |
| author_sort | Peggy S Lai |
| collection | DOAJ |
| description | Endotoxin is a near ubiquitous environmental exposure that that has been associated with both asthma and chronic obstructive pulmonary disease (COPD). These obstructive lung diseases have a complex pathophysiology, making them difficult to study comprehensively in the context of endotoxin. Genome-wide gene expression studies have been used to identify a molecular snapshot of the response to environmental exposures. Identification of differentially expressed genes shared across all published murine models of chronic inhaled endotoxin will provide insight into the biology underlying endotoxin-associated lung disease.We identified three published murine models with gene expression profiling after repeated low-dose inhaled endotoxin. All array data from these experiments were re-analyzed, annotated consistently, and tested for shared genes found to be differentially expressed. Additional functional comparison was conducted by testing for significant enrichment of differentially expressed genes in known pathways. The importance of this gene signature in smoking-related lung disease was assessed using hierarchical clustering in an independent experiment where mice were exposed to endotoxin, smoke, and endotoxin plus smoke.A 101-gene signature was detected in three murine models, more than expected by chance. The three model systems exhibit additional similarity beyond shared genes when compared at the pathway level, with increasing enrichment of inflammatory pathways associated with longer duration of endotoxin exposure. Genes and pathways important in both asthma and COPD were shared across all endotoxin models. Mice exposed to endotoxin, smoke, and smoke plus endotoxin were accurately classified with the endotoxin gene signature.Despite the differences in laboratory, duration of exposure, and strain of mouse used in three experimental models of chronic inhaled endotoxin, surprising similarities in gene expression were observed. The endotoxin component of tobacco smoke may play an important role in disease development. |
| first_indexed | 2024-12-22T11:39:05Z |
| format | Article |
| id | doaj.art-5db50d3ee8434e2ea63891051893356e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T11:39:05Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5db50d3ee8434e2ea63891051893356e2022-12-21T18:27:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6291010.1371/journal.pone.0062910Integrating murine gene expression studies to understand obstructive lung disease due to chronic inhaled endotoxin.Peggy S LaiOliver HofmannRebecca M BaronManuela CernadasQuanxin Ryan MengHerbert S BreslerDavid M BrassIvana V YangDavid A SchwartzDavid C ChristianiWinston HideEndotoxin is a near ubiquitous environmental exposure that that has been associated with both asthma and chronic obstructive pulmonary disease (COPD). These obstructive lung diseases have a complex pathophysiology, making them difficult to study comprehensively in the context of endotoxin. Genome-wide gene expression studies have been used to identify a molecular snapshot of the response to environmental exposures. Identification of differentially expressed genes shared across all published murine models of chronic inhaled endotoxin will provide insight into the biology underlying endotoxin-associated lung disease.We identified three published murine models with gene expression profiling after repeated low-dose inhaled endotoxin. All array data from these experiments were re-analyzed, annotated consistently, and tested for shared genes found to be differentially expressed. Additional functional comparison was conducted by testing for significant enrichment of differentially expressed genes in known pathways. The importance of this gene signature in smoking-related lung disease was assessed using hierarchical clustering in an independent experiment where mice were exposed to endotoxin, smoke, and endotoxin plus smoke.A 101-gene signature was detected in three murine models, more than expected by chance. The three model systems exhibit additional similarity beyond shared genes when compared at the pathway level, with increasing enrichment of inflammatory pathways associated with longer duration of endotoxin exposure. Genes and pathways important in both asthma and COPD were shared across all endotoxin models. Mice exposed to endotoxin, smoke, and smoke plus endotoxin were accurately classified with the endotoxin gene signature.Despite the differences in laboratory, duration of exposure, and strain of mouse used in three experimental models of chronic inhaled endotoxin, surprising similarities in gene expression were observed. The endotoxin component of tobacco smoke may play an important role in disease development.http://europepmc.org/articles/PMC3652821?pdf=render |
| spellingShingle | Peggy S Lai Oliver Hofmann Rebecca M Baron Manuela Cernadas Quanxin Ryan Meng Herbert S Bresler David M Brass Ivana V Yang David A Schwartz David C Christiani Winston Hide Integrating murine gene expression studies to understand obstructive lung disease due to chronic inhaled endotoxin. PLoS ONE |
| title | Integrating murine gene expression studies to understand obstructive lung disease due to chronic inhaled endotoxin. |
| title_full | Integrating murine gene expression studies to understand obstructive lung disease due to chronic inhaled endotoxin. |
| title_fullStr | Integrating murine gene expression studies to understand obstructive lung disease due to chronic inhaled endotoxin. |
| title_full_unstemmed | Integrating murine gene expression studies to understand obstructive lung disease due to chronic inhaled endotoxin. |
| title_short | Integrating murine gene expression studies to understand obstructive lung disease due to chronic inhaled endotoxin. |
| title_sort | integrating murine gene expression studies to understand obstructive lung disease due to chronic inhaled endotoxin |
| url | http://europepmc.org/articles/PMC3652821?pdf=render |
| work_keys_str_mv | AT peggyslai integratingmurinegeneexpressionstudiestounderstandobstructivelungdiseaseduetochronicinhaledendotoxin AT oliverhofmann integratingmurinegeneexpressionstudiestounderstandobstructivelungdiseaseduetochronicinhaledendotoxin AT rebeccambaron integratingmurinegeneexpressionstudiestounderstandobstructivelungdiseaseduetochronicinhaledendotoxin AT manuelacernadas integratingmurinegeneexpressionstudiestounderstandobstructivelungdiseaseduetochronicinhaledendotoxin AT quanxinryanmeng integratingmurinegeneexpressionstudiestounderstandobstructivelungdiseaseduetochronicinhaledendotoxin AT herbertsbresler integratingmurinegeneexpressionstudiestounderstandobstructivelungdiseaseduetochronicinhaledendotoxin AT davidmbrass integratingmurinegeneexpressionstudiestounderstandobstructivelungdiseaseduetochronicinhaledendotoxin AT ivanavyang integratingmurinegeneexpressionstudiestounderstandobstructivelungdiseaseduetochronicinhaledendotoxin AT davidaschwartz integratingmurinegeneexpressionstudiestounderstandobstructivelungdiseaseduetochronicinhaledendotoxin AT davidcchristiani integratingmurinegeneexpressionstudiestounderstandobstructivelungdiseaseduetochronicinhaledendotoxin AT winstonhide integratingmurinegeneexpressionstudiestounderstandobstructivelungdiseaseduetochronicinhaledendotoxin |