Publication

Link between increased cellular senescence and extracellular matrix changes in COPD

Woldhuis, R. R., de Vries, M., Timens, W., van den Berge, M., Demaria, M., Oliver, B. G. G., Heijink, I. H. & Brandsma, C-A., Jul-2020, In : American Journal of Physiology - Lung Cellular and Molecular Physiology. 319, 1, p. L48-L60 13 p.

Research output: Contribution to journalArticleAcademicpeer-review

Copy link to clipboard

Documents

  • Link between increased cellular senescence and extracellular matrix changes in COPD

    Final author's version, 6 MB, PDF document

    Embargo ends: 27/05/2021

    Request copy

  • Link between increased cellular senescence and extracellular matrix changes in COPD

    Final publisher's version, 3 MB, PDF document

    Request copy

DOI

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 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 to 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.

Original languageEnglish
Pages (from-to)L48-L60
Number of pages13
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume319
Issue number1
Early online date2020
Publication statusPublished - Jul-2020

ID: 126101042