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A Senescence Bystander Effect in Human Lung Fibroblasts
Biomedicines. 2021 Sep 4;9(9):1162. doi: 10.3390/biomedicines9091162.
David W Waters 1 2, Michael Schuliga 1, Prabuddha S Pathinayake 3, Lan Wei 1, Hui-Ying Tan 1, Kaj E C Blokland 1 2 4, Jade Jaffar 5, Glen P Westall 5, Janette K Burgess 4, Cecilia M Prêle 6 7, Steven E Mutsaers 6 7, Christopher L Grainge 3, Darryl A Knight 1 2 8
Abstract:
...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.
PMID: 34572347
Free Full-Text: https://www.mdpi.com/2227-9059/9/9/1162/htm