COPD-derived fibroblasts secrete higher levels of senescence-associated secretory phenotype proteins

COPD-derived fibroblasts have increased cellular senescence. Senescent cell accumulation can induce tissue dysfunction by their senescence-associated secretory phenotype (SASP). We aimed to determine the SASP of senescent fibroblasts and COPD-derived lung fibroblasts, including severe, early-onset (SEO)-COPD. SASP protein secretion was measured after paraquat-induced senescence in lung fibroblasts using Olink Proteomics and compared between (SEO-)COPD-derived and control-derived fibroblasts. We identified 124 SASP proteins of senescent lung fibroblasts, of which 42 were secreted at higher levels by COPD-derived fibroblasts and 35 by SEO-COPD-derived fibroblasts compared with controls. Interestingly, the (SEO-)COPD-associated SASP included proteins involved in chronic inflammation, which may contribute to (SEO-)COPD pathogenesis.

[1]  W. Timens,et al.  Link between increased cellular senescence and extracellular matrix changes in COPD. , 2020, American journal of physiology. Lung cellular and molecular physiology.

[2]  L. Ferrucci,et al.  A proteomic atlas of senescence-associated secretomes for aging biomarker development , 2019, bioRxiv.

[3]  Georgia Woods,et al.  Cellular Senescence Is Induced by the Environmental Neurotoxin Paraquat and Contributes to Neuropathology Linked to Parkinson’s Disease , 2018, Cell reports.

[4]  Y. Bossé,et al.  Lung tissue gene-expression signature for the ageing lung in COPD , 2017, Thorax.

[5]  W. Timens,et al.  Lung ageing and COPD: is there a role for ageing in abnormal tissue repair? , 2017, European Respiratory Review.

[6]  O. Eickelberg,et al.  Hallmarks of the ageing lung , 2015, European Respiratory Journal.

[7]  Y. Bossé,et al.  A large lung gene expression study identifying fibulin-5 as a novel player in tissue repair in COPD , 2014, Thorax.

[8]  Manuel Serrano,et al.  Cellular senescence: from physiology to pathology , 2014, Nature Reviews Molecular Cell Biology.

[9]  D. Peeper,et al.  The essence of senescence. , 2010, Genes & development.

[10]  Judith Campisi,et al.  Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor , 2008, PLoS biology.

[11]  Manisha N. Patel,et al.  Mitochondria Are a Major Source of Paraquat-induced Reactive Oxygen Species Production in the Brain* , 2007, Journal of Biological Chemistry.

[12]  Kazuhiro Ito,et al.  Translating Basic Research Into Clinical Practice COPD as a Disease of Accelerated Lung Aging * , 2009 .