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Journal article
Senescence intensifies bleomycin-induced injury in IPF-lung epithelial cells
ERJ open research, Early View
2026
Abstract
Introduction
Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease involving injury and a dysregulated repair response of an ageing epithelium. Here we investigate the contribution of senescence and telomere shortening to bleomycin-induced injury in alveolar epithelial cells (EpCs) derived from lung parenchymal tissue of patients with pulmonary fibrosis (PF), predominantly IPF, in vitro.
Methods
Injury responses of EpCs in air liquid interface (ALI) culture were assessed by ELISA, qPCR and/or immunofluorescence at 48 and 96 h post-bleomycin (30 μg·mL−1) treatment. Telomere length was evaluated by qPCR and corroborated by fluorescence in situ hybridisation (FISH).
Results
Bleomycin treatment increased markers of inflammation (i.e. interleukin-6 and −36γ) and senescence (i.e. p16 and p21) in EpCs from PF patients (PF-EpCs) (p<0.05); responses markedly higher than control EpCs (Ctrl-EpCs). Conversely, the effects of bleomycin on the expression of type I and type II alveolar EpC markers were supressed or down-regulated in cultures of PF-EpCs (when compared to Ctrl-EpCs), whereas the percentage of keratin 17 positive type I and II intermediate EpCs were increased (p<0.05). Telomere length was also significantly shorter in PF- than Ctrl-EpCs at baseline and further reduced post-bleomycin treatment (p<0.05). Induction of telomere shortening by cell passaging augmented bleomycin-induced PF-EpC injury, whereas pharmacological telomerase activation and selected senotherapeutics were protective.
Conclusion
This study provides evidence that senescence-associated telomere shortening increases the susceptibility of IPF-lung EpCs to injury. Our cell-based lung epithelial injury model has utility as a pre-clinical tool for drug discovery and the evaluation of potential senotherapeutics for IPF treatment.
Details
- Title
- Senescence intensifies bleomycin-induced injury in IPF-lung epithelial cells
- Authors/Creators
- Jane Read - University of Newcastle AustraliaAndrew T Reid - Hunter Medical Research InstituteClaire Thomson - University of Newcastle AustraliaMarshall Plit - St Vincent's Hospital SydneyQue Tran LaRoss Mejia - John Hunter HospitalPankaj Saxena - John Hunter HospitalDarryl A Knight - Providence Health Care Research InstituteMuriel Lizé - Boehringer Ingelheim (Germany)Cecilia M Prêle - Murdoch UniversityChristopher L Grainge - University of Newcastle AustraliaHeiko Stahl - Boehringer Ingelheim (Germany)Michael Schuliga - University of Newcastle Australia
- Publication Details
- ERJ open research, Early View
- Publisher
- ERS Publications
- Identifiers
- 991005865254507891
- Copyright
- © The authors 2026.
- Murdoch Affiliation
- School of Medical, Molecular and Forensic Sciences
- Language
- English
- Resource Type
- Journal article
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