Senescence of IPF Lung Fibroblasts Disrupt Alveolar Epithelial Cell Proliferation and Promote Migration in Wound Healing
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 r...
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doaj-c78d3268b80d43e7a397a1b9abe041952020-11-25T03:54:25ZengMDPI AGPharmaceutics1999-49232020-04-011238938910.3390/pharmaceutics12040389Senescence of IPF Lung Fibroblasts Disrupt Alveolar Epithelial Cell Proliferation and Promote Migration in Wound HealingKaj E. C. Blokland0David W. Waters1Michael Schuliga2Jane Read3Simon D. Pouwels4Christopher L. Grainge5Jade Jaffar6Glen Westall7Steven E. Mutsaers8Cecilia M. Prêle9Janette K. Burgess10Darryl A. Knight11School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, AustraliaUniversity of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, 9713 GZ Groningen, The NetherlandsNational Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis, Camperdown, NSW 2050, AustraliaAllergy, Immunology and Respiratory Medicine, Alfred Hospital, Prahran, Vic 3004, AustraliaAllergy, Immunology and Respiratory Medicine, Alfred Hospital, Prahran, Vic 3004, AustraliaCentre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences University of Western Australia, Crawley, WA 6009, AustraliaCentre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences University of Western Australia, Crawley, WA 6009, AustraliaUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, 9713 GZ Groningen, The NetherlandsSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, AustraliaIdiopathic 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.https://www.mdpi.com/1999-4923/12/4/389senescencefibroblastsalveolar epithelial cellfibrosisaberrant repaircell-cycle inhibition |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kaj E. C. Blokland David W. Waters Michael Schuliga Jane Read Simon D. Pouwels Christopher L. Grainge Jade Jaffar Glen Westall Steven E. Mutsaers Cecilia M. Prêle Janette K. Burgess Darryl A. Knight |
spellingShingle |
Kaj E. C. Blokland David W. Waters Michael Schuliga Jane Read Simon D. Pouwels Christopher L. Grainge Jade Jaffar Glen Westall Steven E. Mutsaers Cecilia M. Prêle Janette K. Burgess Darryl A. Knight Senescence of IPF Lung Fibroblasts Disrupt Alveolar Epithelial Cell Proliferation and Promote Migration in Wound Healing Pharmaceutics senescence fibroblasts alveolar epithelial cell fibrosis aberrant repair cell-cycle inhibition |
author_facet |
Kaj E. C. Blokland David W. Waters Michael Schuliga Jane Read Simon D. Pouwels Christopher L. Grainge Jade Jaffar Glen Westall Steven E. Mutsaers Cecilia M. Prêle Janette K. Burgess Darryl A. Knight |
author_sort |
Kaj E. C. Blokland |
title |
Senescence of IPF Lung Fibroblasts Disrupt Alveolar Epithelial Cell Proliferation and Promote Migration in Wound Healing |
title_short |
Senescence of IPF Lung Fibroblasts Disrupt Alveolar Epithelial Cell Proliferation and Promote Migration in Wound Healing |
title_full |
Senescence of IPF Lung Fibroblasts Disrupt Alveolar Epithelial Cell Proliferation and Promote Migration in Wound Healing |
title_fullStr |
Senescence of IPF Lung Fibroblasts Disrupt Alveolar Epithelial Cell Proliferation and Promote Migration in Wound Healing |
title_full_unstemmed |
Senescence of IPF Lung Fibroblasts Disrupt Alveolar Epithelial Cell Proliferation and Promote Migration in Wound Healing |
title_sort |
senescence of ipf lung fibroblasts disrupt alveolar epithelial cell proliferation and promote migration in wound healing |
publisher |
MDPI AG |
series |
Pharmaceutics |
issn |
1999-4923 |
publishDate |
2020-04-01 |
description |
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. |
topic |
senescence fibroblasts alveolar epithelial cell fibrosis aberrant repair cell-cycle inhibition |
url |
https://www.mdpi.com/1999-4923/12/4/389 |
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