Link between increased cellular senescence and extracellular matrix changes in COPD.
Woldhuis, RR
de Vries, M
Timens, W
van den Berge, M
Demaria, M
Oliver, BGG
Heijink, IH
Brandsma, C-A
- Publisher:
- AMER PHYSIOLOGICAL SOC
- Publication Type:
- Journal Article
- Citation:
- American journal of physiology. Lung cellular and molecular physiology, 2020, 319, (1), pp. L48-L60
- Issue Date:
- 2020-07
Closed Access
Filename | Description | Size | |||
---|---|---|---|---|---|
ajplung.00028.2020.pdf | Published version | 3.8 MB | Adobe PDF |
Copyright Clearance Process
- Recently Added
- In Progress
- Closed Access
This item is closed access and not available.
Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Woldhuis, RR | |
dc.contributor.author | de Vries, M | |
dc.contributor.author | Timens, W | |
dc.contributor.author | van den Berge, M | |
dc.contributor.author | Demaria, M | |
dc.contributor.author | Oliver, BGG | |
dc.contributor.author | Heijink, IH | |
dc.contributor.author | Brandsma, C-A | |
dc.date.accessioned | 2020-12-17T03:21:48Z | |
dc.date.available | 2020-12-17T03:21:48Z | |
dc.date.issued | 2020-07 | |
dc.identifier.citation | American journal of physiology. Lung cellular and molecular physiology, 2020, 319, (1), pp. L48-L60 | |
dc.identifier.issn | 1040-0605 | |
dc.identifier.issn | 1522-1504 | |
dc.identifier.uri | http://hdl.handle.net/10453/144799 | |
dc.description.abstract | Chronic obstructive pulmonary disease (COPD) is associated with features of accelerated aging, including cellular senescence, DNA damage, oxidative stress, and extracellular matrix (ECM) changes. We propose that these features are particularly apparent in patients with severe, early-onset (SEO)-COPD. Whether fibroblasts from COPD patients display features of accelerated aging and whether this is also present in relatively young SEO-COPD patients is unknown. Therefore, we aimed to determine markers of aging in (SEO)-COPD-derived lung fibroblasts and investigate the impact on ECM. Aging hallmarks and ECM markers were analyzed in lung fibroblasts from SEO-COPD and older COPD patients and compared with fibroblasts from matched non-COPD groups (n = 9-11 per group), both at normal culture conditions and upon Paraquat-induced senescence. COPD-related differences in senescence and ECM expression were validated in lung tissue. Higher levels of cellular senescence, including senescence-associated β-galactosidase (SA-β-gal)-positive cells (19% for COPD vs. 13% for control) and p16 expression, DNA damage (γ-H2A.X-positive nuclei), and oxidative stress (MGST1) were detected in COPD compared with control-derived fibroblasts. Most effects were also different in SEO-COPD, with SA-β-gal-positive cells only being significant in SEO-COPD vs. matched controls. Lower decorin expression in COPD-derived fibroblasts correlated with higher p16 expression, and this association was confirmed in lung tissue. Paraquat treatment induced cellular senescence along with clear changes in ECM expression, including decorin. Fibroblasts from COPD patients, including SEO-COPD, display higher levels of cellular senescence, DNA damage, and oxidative stress. The association between cellular senescence and ECM expression changes may suggest a link between accelerated aging and ECM dysregulation in COPD. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.publisher | AMER PHYSIOLOGICAL SOC | |
dc.relation | http://purl.org/au-research/grants/nhmrc/APP1110368 | |
dc.relation | Thoracic Society of Australia and New ZealandN/A | |
dc.relation | http://purl.org/au-research/grants/nhmrc/GNT1110368 | |
dc.relation.ispartof | American journal of physiology. Lung cellular and molecular physiology | |
dc.relation.isbasedon | 10.1152/ajplung.00028.2020 | |
dc.rights | info:eu-repo/semantics/closedAccess | |
dc.subject | 0606 Physiology, 1116 Medical Physiology | |
dc.subject.classification | Respiratory System | |
dc.subject.mesh | Lung | |
dc.subject.mesh | Cells, Cultured | |
dc.subject.mesh | Extracellular Matrix | |
dc.subject.mesh | Fibroblasts | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Pulmonary Disease, Chronic Obstructive | |
dc.subject.mesh | DNA Damage | |
dc.subject.mesh | Paraquat | |
dc.subject.mesh | Neuropeptides | |
dc.subject.mesh | Microtubule-Associated Proteins | |
dc.subject.mesh | Age of Onset | |
dc.subject.mesh | Gene Expression Regulation | |
dc.subject.mesh | Oxidative Stress | |
dc.subject.mesh | Adult | |
dc.subject.mesh | Middle Aged | |
dc.subject.mesh | Female | |
dc.subject.mesh | Male | |
dc.subject.mesh | Biomarkers | |
dc.subject.mesh | Cellular Senescence | |
dc.subject.mesh | Lung | |
dc.subject.mesh | Cells, Cultured | |
dc.subject.mesh | Extracellular Matrix | |
dc.subject.mesh | Fibroblasts | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Pulmonary Disease, Chronic Obstructive | |
dc.subject.mesh | DNA Damage | |
dc.subject.mesh | Paraquat | |
dc.subject.mesh | Neuropeptides | |
dc.subject.mesh | Microtubule-Associated Proteins | |
dc.subject.mesh | Age of Onset | |
dc.subject.mesh | Gene Expression Regulation | |
dc.subject.mesh | Oxidative Stress | |
dc.subject.mesh | Adult | |
dc.subject.mesh | Middle Aged | |
dc.subject.mesh | Female | |
dc.subject.mesh | Male | |
dc.subject.mesh | Biomarkers | |
dc.subject.mesh | Cellular Senescence | |
dc.subject.mesh | Adult | |
dc.subject.mesh | Age of Onset | |
dc.subject.mesh | Biomarkers | |
dc.subject.mesh | Cells, Cultured | |
dc.subject.mesh | Cellular Senescence | |
dc.subject.mesh | DNA Damage | |
dc.subject.mesh | Extracellular Matrix | |
dc.subject.mesh | Female | |
dc.subject.mesh | Fibroblasts | |
dc.subject.mesh | Gene Expression Regulation | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Lung | |
dc.subject.mesh | Male | |
dc.subject.mesh | Microtubule-Associated Proteins | |
dc.subject.mesh | Middle Aged | |
dc.subject.mesh | Neuropeptides | |
dc.subject.mesh | Oxidative Stress | |
dc.subject.mesh | Paraquat | |
dc.subject.mesh | Pulmonary Disease, Chronic Obstructive | |
dc.title | Link between increased cellular senescence and extracellular matrix changes in COPD. | |
dc.type | Journal Article | |
utslib.citation.volume | 319 | |
utslib.location.activity | United States | |
utslib.for | 0606 Physiology | |
utslib.for | 1116 Medical Physiology | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Strength - CHT - Health Technologies | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
pubs.organisational-group | /University of Technology Sydney | |
utslib.copyright.status | closed_access | * |
pubs.consider-herdc | false | |
dc.date.updated | 2020-12-17T03:21:40Z | |
pubs.issue | 1 | |
pubs.publication-status | Published | |
pubs.volume | 319 | |
utslib.citation.issue | 1 |
Abstract:
Chronic obstructive pulmonary disease (COPD) is associated with features of accelerated aging, including cellular senescence, DNA damage, oxidative stress, and extracellular matrix (ECM) changes. We propose that these features are particularly apparent in patients with severe, early-onset (SEO)-COPD. Whether fibroblasts from COPD patients display features of accelerated aging and whether this is also present in relatively young SEO-COPD patients is unknown. Therefore, we aimed to determine markers of aging in (SEO)-COPD-derived lung fibroblasts and investigate the impact on ECM. Aging hallmarks and ECM markers were analyzed in lung fibroblasts from SEO-COPD and older COPD patients and compared with fibroblasts from matched non-COPD groups (n = 9-11 per group), both at normal culture conditions and upon Paraquat-induced senescence. COPD-related differences in senescence and ECM expression were validated in lung tissue. Higher levels of cellular senescence, including senescence-associated β-galactosidase (SA-β-gal)-positive cells (19% for COPD vs. 13% for control) and p16 expression, DNA damage (γ-H2A.X-positive nuclei), and oxidative stress (MGST1) were detected in COPD compared with control-derived fibroblasts. Most effects were also different in SEO-COPD, with SA-β-gal-positive cells only being significant in SEO-COPD vs. matched controls. Lower decorin expression in COPD-derived fibroblasts correlated with higher p16 expression, and this association was confirmed in lung tissue. Paraquat treatment induced cellular senescence along with clear changes in ECM expression, including decorin. Fibroblasts from COPD patients, including SEO-COPD, display higher levels of cellular senescence, DNA damage, and oxidative stress. The association between cellular senescence and ECM expression changes may suggest a link between accelerated aging and ECM dysregulation in COPD.
Please use this identifier to cite or link to this item:
Download statistics for the last 12 months
Not enough data to produce graph