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Fibroblast to myofibroblast transition is enhanced by increased cell density

Idiopathic pulmonary fibrosis (IPF) is a chronic disease of the lung caused by a rampant inflammatory response that results in the deposition of excessive extracellular matrix (ECM). IPF patient lungs also develop fibroblastic foci that consist of activated fibroblasts and myofibroblasts. In concert...

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Detalles Bibliográficos
Autores principales: Doolin, Mary T., Smith, Ian M., Stroka, Kimberly M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694087/
https://www.ncbi.nlm.nih.gov/pubmed/34731044
http://dx.doi.org/10.1091/mbc.E20-08-0536
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author Doolin, Mary T.
Smith, Ian M.
Stroka, Kimberly M.
author_facet Doolin, Mary T.
Smith, Ian M.
Stroka, Kimberly M.
author_sort Doolin, Mary T.
collection PubMed
description Idiopathic pulmonary fibrosis (IPF) is a chronic disease of the lung caused by a rampant inflammatory response that results in the deposition of excessive extracellular matrix (ECM). IPF patient lungs also develop fibroblastic foci that consist of activated fibroblasts and myofibroblasts. In concert with ECM deposition, the increased cell density within fibroblastic foci imposes confining forces on lung fibroblasts. In this work, we observed that increased cell density increases the incidence of the fibroblast-to-myofibroblast transition (FMT), but mechanical confinement imposed by micropillars has no effect on FMT incidence. We found that human lung fibroblasts (HLFs) express more α-SMA and deposit more collagen matrix, which are both characteristics of myofibroblasts, in response to TGF-β1 when cells are seeded at a high density compared with a medium or a low density. These results support the hypothesis that HLFs undergo FMT more readily in response to TGF-β1 when cells are densely packed, and this effect could be dependent on increased OB-cadherin expression. This work demonstrates that cell density is an important factor to consider when modelling IPF in vitro, and it may suggest decreasing cell density within fibroblastic foci as a strategy to reduce IPF burden.
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spelling pubmed-86940872022-02-16 Fibroblast to myofibroblast transition is enhanced by increased cell density Doolin, Mary T. Smith, Ian M. Stroka, Kimberly M. Mol Biol Cell Articles Idiopathic pulmonary fibrosis (IPF) is a chronic disease of the lung caused by a rampant inflammatory response that results in the deposition of excessive extracellular matrix (ECM). IPF patient lungs also develop fibroblastic foci that consist of activated fibroblasts and myofibroblasts. In concert with ECM deposition, the increased cell density within fibroblastic foci imposes confining forces on lung fibroblasts. In this work, we observed that increased cell density increases the incidence of the fibroblast-to-myofibroblast transition (FMT), but mechanical confinement imposed by micropillars has no effect on FMT incidence. We found that human lung fibroblasts (HLFs) express more α-SMA and deposit more collagen matrix, which are both characteristics of myofibroblasts, in response to TGF-β1 when cells are seeded at a high density compared with a medium or a low density. These results support the hypothesis that HLFs undergo FMT more readily in response to TGF-β1 when cells are densely packed, and this effect could be dependent on increased OB-cadherin expression. This work demonstrates that cell density is an important factor to consider when modelling IPF in vitro, and it may suggest decreasing cell density within fibroblastic foci as a strategy to reduce IPF burden. The American Society for Cell Biology 2021-12-01 /pmc/articles/PMC8694087/ /pubmed/34731044 http://dx.doi.org/10.1091/mbc.E20-08-0536 Text en © 2021 Doolin et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License.
spellingShingle Articles
Doolin, Mary T.
Smith, Ian M.
Stroka, Kimberly M.
Fibroblast to myofibroblast transition is enhanced by increased cell density
title Fibroblast to myofibroblast transition is enhanced by increased cell density
title_full Fibroblast to myofibroblast transition is enhanced by increased cell density
title_fullStr Fibroblast to myofibroblast transition is enhanced by increased cell density
title_full_unstemmed Fibroblast to myofibroblast transition is enhanced by increased cell density
title_short Fibroblast to myofibroblast transition is enhanced by increased cell density
title_sort fibroblast to myofibroblast transition is enhanced by increased cell density
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694087/
https://www.ncbi.nlm.nih.gov/pubmed/34731044
http://dx.doi.org/10.1091/mbc.E20-08-0536
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