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Extracellular matrix remodeling associated with bleomycin-induced lung injury supports pericyte-to-myofibroblast transition

Of the many origins of pulmonary myofibroblasts, microvascular pericytes are a known source. Prior literature has established the ability of pericytes to transition into myofibroblasts, but provide limited insight into molecular cues that drive this process during lung injury repair and fibrosis. Fi...

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Autores principales: Hannan, Riley T., Miller, Andrew E., Hung, Ruei-Chun, Sano, Catherine, Peirce, Shayn M., Barker, Thomas H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233458/
https://www.ncbi.nlm.nih.gov/pubmed/34195593
http://dx.doi.org/10.1016/j.mbplus.2020.100056
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author Hannan, Riley T.
Miller, Andrew E.
Hung, Ruei-Chun
Sano, Catherine
Peirce, Shayn M.
Barker, Thomas H.
author_facet Hannan, Riley T.
Miller, Andrew E.
Hung, Ruei-Chun
Sano, Catherine
Peirce, Shayn M.
Barker, Thomas H.
author_sort Hannan, Riley T.
collection PubMed
description Of the many origins of pulmonary myofibroblasts, microvascular pericytes are a known source. Prior literature has established the ability of pericytes to transition into myofibroblasts, but provide limited insight into molecular cues that drive this process during lung injury repair and fibrosis. Fibronectin and RGD-binding integrins have long been considered pro-fibrotic factors in myofibroblast biology, and here we test the hypothesis that these known myofibroblast cues coordinate pericyte-to-myofibroblast transitions. Specifically, we hypothesized that αvβ3 integrin engagement on fibronectin induces pericyte transition into myofibroblastic phenotypes in the murine bleomycin lung injury model. Myosin Heavy Chain 11 (Myh11)-CreERT2 lineage tracing in transgenic mice allows identification of cells of pericyte origin and provides a robust tool for isolating pericytes from tissues for further evaluation. We used this murine model to track and characterize pericyte behaviors during tissue repair. The majority of Myh11 lineage-positive cells are positive for the pericyte surface markers, PDGFRβ (55%) and CD146 (69%), and display typical pericyte morphology with spatial apposition to microvascular networks. After intratracheal bleomycin treatment of mice, Myh11 lineage-positive cells showed significantly increased contractile and secretory markers, as well as αv integrin expression. According to RNASeq measurements, many disease and tissue-remodeling genesets were upregulated in Myh11 lineage-positive cells in response to bleomycin-induced lung injury. In vitro, blocking αvβ3 binding through cycloRGDfK prevented expression of the myofibroblastic marker αSMA relative to controls. In response to RGD-containing provisional matrix proteins present in lung injury, pericytes may alter their integrin profile.
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spelling pubmed-82334582021-06-29 Extracellular matrix remodeling associated with bleomycin-induced lung injury supports pericyte-to-myofibroblast transition Hannan, Riley T. Miller, Andrew E. Hung, Ruei-Chun Sano, Catherine Peirce, Shayn M. Barker, Thomas H. Matrix Biol Plus Article Of the many origins of pulmonary myofibroblasts, microvascular pericytes are a known source. Prior literature has established the ability of pericytes to transition into myofibroblasts, but provide limited insight into molecular cues that drive this process during lung injury repair and fibrosis. Fibronectin and RGD-binding integrins have long been considered pro-fibrotic factors in myofibroblast biology, and here we test the hypothesis that these known myofibroblast cues coordinate pericyte-to-myofibroblast transitions. Specifically, we hypothesized that αvβ3 integrin engagement on fibronectin induces pericyte transition into myofibroblastic phenotypes in the murine bleomycin lung injury model. Myosin Heavy Chain 11 (Myh11)-CreERT2 lineage tracing in transgenic mice allows identification of cells of pericyte origin and provides a robust tool for isolating pericytes from tissues for further evaluation. We used this murine model to track and characterize pericyte behaviors during tissue repair. The majority of Myh11 lineage-positive cells are positive for the pericyte surface markers, PDGFRβ (55%) and CD146 (69%), and display typical pericyte morphology with spatial apposition to microvascular networks. After intratracheal bleomycin treatment of mice, Myh11 lineage-positive cells showed significantly increased contractile and secretory markers, as well as αv integrin expression. According to RNASeq measurements, many disease and tissue-remodeling genesets were upregulated in Myh11 lineage-positive cells in response to bleomycin-induced lung injury. In vitro, blocking αvβ3 binding through cycloRGDfK prevented expression of the myofibroblastic marker αSMA relative to controls. In response to RGD-containing provisional matrix proteins present in lung injury, pericytes may alter their integrin profile. Elsevier 2020-12-30 /pmc/articles/PMC8233458/ /pubmed/34195593 http://dx.doi.org/10.1016/j.mbplus.2020.100056 Text en © 2020 Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Hannan, Riley T.
Miller, Andrew E.
Hung, Ruei-Chun
Sano, Catherine
Peirce, Shayn M.
Barker, Thomas H.
Extracellular matrix remodeling associated with bleomycin-induced lung injury supports pericyte-to-myofibroblast transition
title Extracellular matrix remodeling associated with bleomycin-induced lung injury supports pericyte-to-myofibroblast transition
title_full Extracellular matrix remodeling associated with bleomycin-induced lung injury supports pericyte-to-myofibroblast transition
title_fullStr Extracellular matrix remodeling associated with bleomycin-induced lung injury supports pericyte-to-myofibroblast transition
title_full_unstemmed Extracellular matrix remodeling associated with bleomycin-induced lung injury supports pericyte-to-myofibroblast transition
title_short Extracellular matrix remodeling associated with bleomycin-induced lung injury supports pericyte-to-myofibroblast transition
title_sort extracellular matrix remodeling associated with bleomycin-induced lung injury supports pericyte-to-myofibroblast transition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233458/
https://www.ncbi.nlm.nih.gov/pubmed/34195593
http://dx.doi.org/10.1016/j.mbplus.2020.100056
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