- Title
- A senescence bystander effect in human lung fibroblasts
- Creator
- Waters, David W.; Schuliga, Michael; Mutsaers, Steven E.; Grainge, Christopher L.; Knight, Darryl A.; Pathinayake, Prabuddha S.; Wei, Lan; Tan, Hui-Ying; Blokland, Kaj E. C.; Jaffar, Jade; Westall, Glen P.; Burgess, Janette K.; Prele, Cecilia M.
- Relation
- NHMRC.1099569 http://purl.org/au-research/grants/nhmrc/1099569
- Relation
- Biomedicines Vol. 9, Issue 9
- Publisher Link
- http://dx.doi.org/10.3390/biomedicines9091162
- Publisher
- MDPI AG
- Resource Type
- journal article
- Date
- 2021
- Description
- 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
- Subject
- collagen; idiopathic pulmonary fibrosis (IPF); lung fibroblasts; senescence
- Identifier
- http://hdl.handle.net/1959.13/1457767
- Identifier
- uon:45373
- Identifier
- ISSN:2227-9059
- Rights
- © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
- Language
- eng
- Full Text
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