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Melo-Narváez, M.C ; Bramey, N. ; See, F. ; Heinzelmann, K. ; Ballester, B. ; Steinchen, C. ; Jain, E. ; Federl, K. ; Hu, Q.* ; Dhakad, D. ; Behr, J.* ; Eickelberg, O.* ; Yildirim, A.Ö. ; Königshoff, M.* ; Lehmann, M.

Stimuli-specific senescence of primary human lung fibroblasts modulates alveolar stem cell function.

Cells 13:1129 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Aging is the main risk factor for chronic lung diseases (CLDs) including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Accordingly, hallmarks of aging like cellular senescence are increased in these patients in different lung cell types including fibroblasts. However, little is known about the different triggers that induce a senescence phenotype in different disease backgrounds and its role in CLD pathogenesis. Therefore, we characterized senescence in primary human lung fibroblasts (phLF) from control, IPF, or COPD patients at baseline and after exposure to disease-relevant insults (H2O2, bleomycin, TGF-β1) and studied their capacity to support progenitor cell potential in a lung organoid model. Bulk-RNA sequencing revealed that phLF from IPF and COPD activate different transcriptional programs but share a similar senescence phenotype at baseline. Moreover, H2O2 and bleomycin but not TGF-β1 induced senescence in phLF from different disease origins. Exposure to different triggers resulted in distinct senescence programs in phLF characterized by different SASP profiles. Finally, co-culture with bleomycin- and H2O2-treated phLF reduced the progenitor cell potential of alveolar epithelial progenitor cells. In conclusion, phLF from COPD and IPF share a conserved senescence response that varies depending on the insult and impairs alveolar epithelial progenitor capacity ex vivo.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Aging ; Cellular Senescence ; Chronic Lung Diseases ; Fibroblasts; Mediator
ISSN (print) / ISBN 2073-4409
e-ISSN 2073-4409
Zeitschrift Cells
Quellenangaben Band: 13, Heft: 13, Seiten: , Artikelnummer: 1129 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Institut(e) Lung Health and Immunity (LHI)
Institute of Lung Biology (LHI)
Förderungen Alexander von Humbolt