Journal article
Senescence of IPF lung fibroblasts disrupt Alveolar Epithelial Cell Proliferation and promote migration in wound healing
Pharmaceutics, Vol.12(4), Art. 389
2020
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by excessive accumulation of lung fibroblasts (LFs) and collagen in the lung parenchyma. The mechanisms that underlie IPF pathophysiology are thought to reflect repeated alveolar epithelial injury leading to an aberrant wound repair response. Recent work has shown that IPF-LFs display increased characteristics of senescence including growth arrest and a senescence-associated secretory phenotype (SASP) suggesting that senescent LFs contribute to dysfunctional wound repair process. Here, we investigated the influence of senescent LFs on alveolar epithelial cell repair responses in a co-culture system. Alveolar epithelial cell proliferation was attenuated when in co-culture with cells or conditioned media from, senescence-induced control LFs or IPF-LFs. Cell-cycle analyses showed that a larger number of epithelial cells were arrested in G2/M phase when co-cultured with IPF-LFs, than in monoculture. Paradoxically, the presence of LFs resulted in increased A549 migration after mechanical injury. Our data suggest that senescent LFs may contribute to aberrant re-epithelialization by inhibiting proliferation in IPF.
Details
- Title
- Senescence of IPF lung fibroblasts disrupt Alveolar Epithelial Cell Proliferation and promote migration in wound healing
- Authors/Creators
- K.E.C. Blokland (Author/Creator) - University of Newcastle AustraliaD.W. Waters (Author/Creator) - National Health and Medical Research CouncilM. Schuliga (Author/Creator) - University of Newcastle AustraliaJ. Read (Author/Creator) - University of Newcastle AustraliaS.D. Pouwels (Author/Creator) - University Medical Center GroningenC.L. Grainge (Author/Creator) - National Health and Medical Research CouncilJ. Jaffar (Author/Creator) - The Alfred HospitalG. Westall (Author/Creator) - The Alfred HospitalS.E. Mutsaers (Author/Creator) - Institute for Respiratory HealthC.M. Prêle (Author/Creator) - Institute for Respiratory HealthJ.K. Burgess (Author/Creator) - University Medical Center GroningenD.A. Knight (Author/Creator) - National Health and Medical Research Council
- Publication Details
- Pharmaceutics, Vol.12(4), Art. 389
- Publisher
- MDPI
- Identifiers
- 991005546012407891
- Copyright
- © 2020 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
- Pharmacology & Pharmacy
- ESI research areas
- Pharmacology & Toxicology