Senescence of ipf lung fibroblasts disrupt alveolar epithelial cell proliferation and promote migration in wound healing

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

doi:10.3390/pharmaceutics12040389

Senescence of ipf lung fibroblasts disrupt alveolar epithelial cell proliferation and promote migration in wound healing

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

Immunology Alfred Hospital

Research output: Contribution to journal › Article › Research › peer-review

36 Citations (Scopus)

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.

Original language	English
Article number	389
Number of pages	11
Journal	Pharmaceutics
Volume	12
Issue number	4
DOIs	https://doi.org/10.3390/pharmaceutics12040389
Publication status	Published - Apr 2020

Keywords

Aberrant repair
Alveolar epithelial cell
Cell-cycle inhibition
Fibroblasts
Fibrosis
Senescence

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10.3390/pharmaceutics12040389Licence: CC BY

315738484-oaFinal published version, 1.11 MBLicence: CC BY

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Blokland, K. E. C., Waters, D. W., Schuliga, M., Read, J., Pouwels, S. D., Grainge, C. L., Jaffar, J., Westall, G., Mutsaers, S. E., Prêle, C. M., Burgess, J. K., & Knight, D. A. (2020). Senescence of ipf lung fibroblasts disrupt alveolar epithelial cell proliferation and promote migration in wound healing. Pharmaceutics, 12(4), Article 389. https://doi.org/10.3390/pharmaceutics12040389

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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.",

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author = "Blokland, {Kaj E.C.} and Waters, {David W.} and Michael Schuliga and Jane Read and Pouwels, {Simon D.} and Grainge, {Christopher L.} and Jade Jaffar and Glen Westall and Mutsaers, {Steven E.} and Pr{\^e}le, {Cecilia M.} and Burgess, {Janette K.} and Knight, {Darryl A.}",

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AU - Pouwels, Simon D.

AU - Grainge, Christopher L.

AU - Jaffar, Jade

AU - Westall, Glen

AU - Mutsaers, Steven E.

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AU - Burgess, Janette K.

AU - Knight, Darryl A.

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AB - 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.

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Senescence of ipf lung fibroblasts disrupt alveolar epithelial cell proliferation and promote migration in wound healing

Abstract

Keywords

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Other files and links

Centre for Research Excellence in Pulmonary Fibrosis. A comprehensive and integrated clinical research program for PF: transforming the approach to PF in Australia

Fibroblast Senescence as a driver of pulmonary fibrosis

Cite this

Senescence of ipf lung fibroblasts disrupt alveolar epithelial cell proliferation and promote migration in wound healing

Abstract

Keywords

Access to Document

Other files and links

Projects

Centre for Research Excellence in Pulmonary Fibrosis. A comprehensive and integrated clinical research program for PF: transforming the approach to PF in Australia

Fibroblast Senescence as a driver of pulmonary fibrosis

Cite this