Abstract
AbstractAging is the main risk factor for chronic lung diseases including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Accordingly, hallmarks of aging such as cellular senescence are increased in different cell types such as fibroblasts in the lungs of these patients. However, whether the senescent phenotype of fibroblasts derived from IPF or COPD differs is still unknown. Therefore, we characterized senescence at baseline and after exposure to disease-relevant insults (H2O2, bleomycin, and TGF-β1) in cultured primary human lung fibroblasts (phLF) from control donors, IPF, or COPD patients. We found that phLF from different disease-origins have a low baseline senescence. H2O2and bleomycin treatment induced a senescent phenotype in phLF whereas TGF-β1 only had a pro-fibrotic effect. Interestingly, we did not observe any differences in susceptibility to senescence induction in phLF based on disease origin. However, exposure to different stimuli resulted in different senescent programs in phLF. Moreover, senescent phLF reduced colony formation efficiency of alveolar epithelial progenitor cells. In conclusion, the senescent phenotype of phLF is mainly determined by the senescence inducer and impairs alveolar epithelial progenitor capacityin vitro.
Publisher
Cold Spring Harbor Laboratory
Reference48 articles.
1. Momtazmanesh S , Moghaddam SS , Ghamari SH , Rad EM , Rezaei N , Shobeiri P , et al. Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019. eClinicalMedicine [Internet]. 2023 May 1 [cited 2023 Jun 24];59. Available from: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00113-X/fulltext
2. Chronic obstructive pulmonary disease;Lancet Lond Engl,2017
3. Risk factors and early origins of chronic obstructive pulmonary disease;Lancet Lond Engl,2015
4. Idiopathic Pulmonary Fibrosis
5. Renal cell carcinoma
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