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

Link between increased cellular senescence and extracellular matrix changes in COPD. Am J Physiol Lung Cell Mol Physiol. 2020 May 27;: Authors: Woldhuis RR, de Vries M, Timens W, van den Berge M, Demaria M, Oliver BGG, Heijink IH, Brandsma CA Abstract 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-Î...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research