Journal article
Alveolar epithelial wound repair is delayed by scenescent lung fibroblasts in IPF
Mechanisms of lung injury and repair, Vol.54(Suppl. 63), PA596
2019
Abstract
Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by excessive accumulation of fibroblasts (fbs) and collagen in lung parenchyma. In IPF it is thought repeated alveolar epithelial (epi) cell injury leads to aberrant re-epithelialisation. IPF fbs demonstrate increased signs of senescence including growth arrest and an activated secretory profile. This study aimed to examine the effect of senescent lung Fbs on the growth and wound repair response of alveolar epi cells.
Methods: Primary human fbs were established from lung tissue of patients with (IPF-Fbs) or without IPF (Ctrl-Fbs). Ctrl-fb were treated with H202 (150 µM, 2h) followed by recovery for 3 days. A549 Epi cells in transwell inserts were cultured ± fbs conditioned media (CM), or co-cultured with fbs with 5% FCS. After 48 hrs A549 cells were harvested for counting and cycle-analysis. Migratory capacity of Epi cells was evaluated using a scratch-wound assay.
Results: Fibroblast senescence was confirmed by increased expression of p21 and senescence-associated β-galactosidase activity. A549 proliferation was attenuated in co-culture with or after transfer of CM from H2O2-treated compared to non-senescent Ctrl-Fbs by 20% (P<0.05). A similar effect was seen with IPF-fbs. Cell-cycle analysis indicated significantly more epi cells (P<0.05) co-cultured with IPF-Fbs were arrested in the G2/M phase. Epithelial cell migration was significantly attenuated in the presence of IPF-Fbs but was amplified with Ctrl-Fbs.
Conclusion: Secreted factors from senescent and/or IPF-fbs delay repair of alveolar epi cells. These data suggest that senescent fbs contribute to IPF pathology by impeding alveolar epi cell regeneration.
Details
- Title
- Alveolar epithelial wound repair is delayed by scenescent lung fibroblasts in IPF
- Authors/Creators
- K. Blokland (Author/Creator)D. Waters (Author/Creator) - University of Newcastle AustraliaM. Schuliga (Author/Creator) - University of Newcastle AustraliaS. Pouwels (Author/Creator) - University Medical Center GroningenC. Grainge (Author/Creator) - University of Newcastle AustraliaS. Mutsaers (Author/Creator) - The University of Western AustraliaC. Prêle (Author/Creator) - The University of Western AustraliaG. Westall (Author/Creator) - Biosecurity AustraliaJ. Jaffar (Author/Creator) - Biosecurity AustraliaD. Knight (Author/Creator) - University of Newcastle AustraliaJ. Burgess (Author/Creator) - University Medical Center Groningen
- Publication Details
- Mechanisms of lung injury and repair, Vol.54(Suppl. 63), PA596
- Publisher
- European Respiratory Society
- Identifiers
- 991005541168907891
- Copyright
- © 2019 The Authors.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.208 Vasculitis & Autoimmune Disorders
- 1.208.1262 Idiopathic Pulmonary Fibrosis
- Web Of Science research areas
- Respiratory System
- ESI research areas
- Clinical Medicine