Journal article
A senescence bystander effect in human lung fibroblasts
Biomedicines, Vol.9(9), Art. 1162
2021
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterised by a dense fibrosing of the lung parenchyma. An association between IPF and cellular senescence is well established and several studies now describe a higher abundance of senescent fibroblasts and epithelial cells in the lungs of IPF patients compared with age-matched controls. The cause of this abnormal accumulation of senescent cells is unknown but evidence suggests that, once established, senescence can be transferred from senescent to non-senescent cells. In this study, we investigated whether senescent human lung fibroblasts (LFs) and alveolar epithelial cells (AECs) could induce a senescent-like phenotype in “naïve” non-senescent LFs in vitro. Primary cultures of LFs from adult control donors (Ctrl-LFs) with a low baseline of senescence were exposed to conditioned medium (CM) from: (i) Ctrl-LFs induced to become senescent using H2O2 or etoposide; (ii) LFs derived from IPF patients (IPF-LFs) with a high baseline of senescence; or (iii) senescence-induced A549 cells, an AEC line. Additionally, ratios of non-senescent Ctrl-LFs and senescence-induced Ctrl-LFs (100:0, 0:100, 50:50, 90:10, 99:1) were co-cultured and their effect on induction of senescence measured. We demonstrated that exposure of naïve non-senescent Ctrl-LFs to CM from senescence-induced Ctrl-LFs and AECs and IPF-LFs increased the markers of senescence including nuclear localisation of phosphorylated-H2A histone family member X (H2AXγ) and expression of p21, IL-6 and IL-8 in Ctrl-LFs. Additionally, co-cultures of non-senescent and senescence-induced Ctrl-LFs induced a senescent-like phenotype in the non-senescent cells. These data suggest that the phenomenon of “senescence-induced senescence” can occur in vitro in primary cultures of human LFs, and provides a possible explanation for the abnormal abundance of senescent cells in the lungs of IPF patients.
Details
- Title
- A senescence bystander effect in human lung fibroblasts
- Authors/Creators
- D.W. Waters (Author/Creator) - University of Newcastle AustraliaM. Schuliga (Author/Creator) - University of Newcastle AustraliaP.S. Pathinayake (Author/Creator) - University of Newcastle AustraliaL. Wei (Author/Creator) - University of Newcastle AustraliaH-Y Tan (Author/Creator) - University of Newcastle AustraliaK.E.C. Blokland (Author/Creator) - University of Newcastle AustraliaJ. Jaffar (Author/Creator) - The Alfred HospitalG.P. Westall (Author/Creator) - The Alfred HospitalJ.K. Burgess (Author/Creator) - University Medical Center GroningenC.M. Prêle (Author/Creator) - Institute for Respiratory HealthS.E. Mutsaers (Author/Creator) - Institute for Respiratory HealthC.L. Grainge (Author/Creator) - University of Newcastle AustraliaD.A. Knight (Author/Creator) - National Health and Medical Research Council
- Publication Details
- Biomedicines, Vol.9(9), Art. 1162
- Publisher
- MDPI
- Identifiers
- 991005541557307891
- Copyright
- © 2022 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
- Biochemistry & Molecular Biology
- Medicine, Research & Experimental
- Pharmacology & Pharmacy
- ESI research areas
- Pharmacology & Toxicology