Reduced expression of the Ion channel CFTR contributes to airspace enlargement as a consequence of aging and in response to cigarette smoke in mice
Abstract Chronic Obstructive Pulmonary Disease (COPD) is a complex disease resulting in respiratory failure and represents the third leading cause of global death. The two classical phenotypes of COPD are chronic bronchitis and emphysema. Owing to similarities between chronic bronchitis and the auto...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-09-01
|
| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12931-019-1170-3 |
| _version_ | 1819088177095245824 |
|---|---|
| author | Jack H. Wellmerling Sheng-Wei Chang Eunsoo Kim Wissam H. Osman Prosper N. Boyaka Michael T. Borchers Estelle Cormet-Boyaka |
| author_facet | Jack H. Wellmerling Sheng-Wei Chang Eunsoo Kim Wissam H. Osman Prosper N. Boyaka Michael T. Borchers Estelle Cormet-Boyaka |
| author_sort | Jack H. Wellmerling |
| collection | DOAJ |
| description | Abstract Chronic Obstructive Pulmonary Disease (COPD) is a complex disease resulting in respiratory failure and represents the third leading cause of global death. The two classical phenotypes of COPD are chronic bronchitis and emphysema. Owing to similarities between chronic bronchitis and the autosomal-recessive disease Cystic Fibrosis (CF), a significant body of research addresses the hypothesis that dysfunctional CF Transmembrane Conductance Regulator (CFTR) is implicated in the pathogenesis of COPD. Much less attention has been given to emphysema in this context, despite similarities between the two diseases. These include early-onset cellular senescence, similar comorbidities, and the finding that CF patients develop emphysema as they age. To determine a potential role for CFTR dysfunction in the development of emphysema, Cftr +/+ (Wild-type; WT), Cftr +/− (heterozygous), and Cftr −/− (knock-out; KO) mice were aged or exposed to cigarette smoke and analyzed for airspace enlargement. Aged knockout mice demonstrated increased alveolar size compared to age-matched wild-type and heterozygous mice. Furthermore, both heterozygous and knockout mice developed enlarged alveoli compared to their wild-type counterparts following chronic smoke exposure. Taken into consideration with previous findings that cigarette smoke leads to reduced CFTR function, our findings suggest that decreased CFTR expression sensitizes the lung to the effects of cigarette smoke. These findings may caution normally asymptomatic CF carriers against exposure to cigarette smoke; as well as highlight emphysema as a future challenge for CF patients as they continue to live longer. More broadly, our data, along with clinical findings, may implicate CFTR dysfunction in a pathology resembling accelerated aging. |
| first_indexed | 2024-12-21T21:47:53Z |
| format | Article |
| id | doaj.art-3eff4f5940c04a55ab4e1f073ddcfead |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-21T21:47:53Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-3eff4f5940c04a55ab4e1f073ddcfead2022-12-21T18:49:11ZengBMCRespiratory Research1465-993X2019-09-012011610.1186/s12931-019-1170-3Reduced expression of the Ion channel CFTR contributes to airspace enlargement as a consequence of aging and in response to cigarette smoke in miceJack H. Wellmerling0Sheng-Wei Chang1Eunsoo Kim2Wissam H. Osman3Prosper N. Boyaka4Michael T. Borchers5Estelle Cormet-Boyaka6Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State UniversityDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State UniversityDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State UniversityDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State UniversityDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State UniversityDepartment of Internal Medicine, College of Medicine, University of CincinnatiDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State UniversityAbstract Chronic Obstructive Pulmonary Disease (COPD) is a complex disease resulting in respiratory failure and represents the third leading cause of global death. The two classical phenotypes of COPD are chronic bronchitis and emphysema. Owing to similarities between chronic bronchitis and the autosomal-recessive disease Cystic Fibrosis (CF), a significant body of research addresses the hypothesis that dysfunctional CF Transmembrane Conductance Regulator (CFTR) is implicated in the pathogenesis of COPD. Much less attention has been given to emphysema in this context, despite similarities between the two diseases. These include early-onset cellular senescence, similar comorbidities, and the finding that CF patients develop emphysema as they age. To determine a potential role for CFTR dysfunction in the development of emphysema, Cftr +/+ (Wild-type; WT), Cftr +/− (heterozygous), and Cftr −/− (knock-out; KO) mice were aged or exposed to cigarette smoke and analyzed for airspace enlargement. Aged knockout mice demonstrated increased alveolar size compared to age-matched wild-type and heterozygous mice. Furthermore, both heterozygous and knockout mice developed enlarged alveoli compared to their wild-type counterparts following chronic smoke exposure. Taken into consideration with previous findings that cigarette smoke leads to reduced CFTR function, our findings suggest that decreased CFTR expression sensitizes the lung to the effects of cigarette smoke. These findings may caution normally asymptomatic CF carriers against exposure to cigarette smoke; as well as highlight emphysema as a future challenge for CF patients as they continue to live longer. More broadly, our data, along with clinical findings, may implicate CFTR dysfunction in a pathology resembling accelerated aging.http://link.springer.com/article/10.1186/s12931-019-1170-3CFTREmphysemaSmokingAging |
| spellingShingle | Jack H. Wellmerling Sheng-Wei Chang Eunsoo Kim Wissam H. Osman Prosper N. Boyaka Michael T. Borchers Estelle Cormet-Boyaka Reduced expression of the Ion channel CFTR contributes to airspace enlargement as a consequence of aging and in response to cigarette smoke in mice Respiratory Research CFTR Emphysema Smoking Aging |
| title | Reduced expression of the Ion channel CFTR contributes to airspace enlargement as a consequence of aging and in response to cigarette smoke in mice |
| title_full | Reduced expression of the Ion channel CFTR contributes to airspace enlargement as a consequence of aging and in response to cigarette smoke in mice |
| title_fullStr | Reduced expression of the Ion channel CFTR contributes to airspace enlargement as a consequence of aging and in response to cigarette smoke in mice |
| title_full_unstemmed | Reduced expression of the Ion channel CFTR contributes to airspace enlargement as a consequence of aging and in response to cigarette smoke in mice |
| title_short | Reduced expression of the Ion channel CFTR contributes to airspace enlargement as a consequence of aging and in response to cigarette smoke in mice |
| title_sort | reduced expression of the ion channel cftr contributes to airspace enlargement as a consequence of aging and in response to cigarette smoke in mice |
| topic | CFTR Emphysema Smoking Aging |
| url | http://link.springer.com/article/10.1186/s12931-019-1170-3 |
| work_keys_str_mv | AT jackhwellmerling reducedexpressionoftheionchannelcftrcontributestoairspaceenlargementasaconsequenceofagingandinresponsetocigarettesmokeinmice AT shengweichang reducedexpressionoftheionchannelcftrcontributestoairspaceenlargementasaconsequenceofagingandinresponsetocigarettesmokeinmice AT eunsookim reducedexpressionoftheionchannelcftrcontributestoairspaceenlargementasaconsequenceofagingandinresponsetocigarettesmokeinmice AT wissamhosman reducedexpressionoftheionchannelcftrcontributestoairspaceenlargementasaconsequenceofagingandinresponsetocigarettesmokeinmice AT prospernboyaka reducedexpressionoftheionchannelcftrcontributestoairspaceenlargementasaconsequenceofagingandinresponsetocigarettesmokeinmice AT michaeltborchers reducedexpressionoftheionchannelcftrcontributestoairspaceenlargementasaconsequenceofagingandinresponsetocigarettesmokeinmice AT estellecormetboyaka reducedexpressionoftheionchannelcftrcontributestoairspaceenlargementasaconsequenceofagingandinresponsetocigarettesmokeinmice |