Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration

Abstract Systemic sclerosis (SSc) is a spreading fibrotic disease affecting the skin and internal organs. We aimed to model pathogenic fibroblast migration in SSc in order to identify enhancing factors, measure the effect of migrating cells on underlying extracellular matrix (ECM) and test possible...

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Autores principales:	Bahja Ahmed Abdi, Henry Lopez, Sarah Karrar, Elisabetta Renzoni, Athol Wells, Angela Tam, Oseme Etomi, J. Justin Hsuan, George R. Martin, Xu Shiwen, Christopher P. Denton, David Abraham, Richard Stratton
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6d882f743d80403ea27006239ee20cc9
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spelling	oai:doaj.org-article:6d882f743d80403ea27006239ee20cc92021-12-02T11:52:17ZUse of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration10.1038/s41598-017-02621-32045-2322https://doaj.org/article/6d882f743d80403ea27006239ee20cc92017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02621-3https://doaj.org/toc/2045-2322Abstract Systemic sclerosis (SSc) is a spreading fibrotic disease affecting the skin and internal organs. We aimed to model pathogenic fibroblast migration in SSc in order to identify enhancing factors, measure the effect of migrating cells on underlying extracellular matrix (ECM) and test possible therapeutic inhibitors. Novel patterned collagen substrates were used to investigate alignment and migration of skin and lung fibroblasts from SSc patients and healthy controls. Normal lung but not skin fibroblasts consistently elongated and aligned with underlying collagen and migrated dependent on PDGF or serum. SSc lung fibroblasts remained growth factor dependent, did not migrate more rapidly and were less restricted to alignment of the collagen. Multiple collagen proline and lysine-modifying enzymes were identified in SSc but not control fibroblast extracellular matrix preparations, indicating differential levels of ECM modification by the diseased cells. Profiling of migrating cells revealed a possible SCF/c-Kit paracrine mechanism contributing to migration via a subpopulation of cells. Heparin, which binds ligands including PDGF and SCF, and imatininib which blocks downstream tyrosine kinase receptors, both inhibited lung fibroblast migration individually but showed synergy in SSc cells. Pathologic lung fibroblasts from SSc patients modify ECM during migration but remain growth factor dependent and sensitive to inhibitors.Bahja Ahmed AbdiHenry LopezSarah KarrarElisabetta RenzoniAthol WellsAngela TamOseme EtomiJ. Justin HsuanGeorge R. MartinXu ShiwenChristopher P. DentonDavid AbrahamRichard StrattonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bahja Ahmed Abdi Henry Lopez Sarah Karrar Elisabetta Renzoni Athol Wells Angela Tam Oseme Etomi J. Justin Hsuan George R. Martin Xu Shiwen Christopher P. Denton David Abraham Richard Stratton Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration
description	Abstract Systemic sclerosis (SSc) is a spreading fibrotic disease affecting the skin and internal organs. We aimed to model pathogenic fibroblast migration in SSc in order to identify enhancing factors, measure the effect of migrating cells on underlying extracellular matrix (ECM) and test possible therapeutic inhibitors. Novel patterned collagen substrates were used to investigate alignment and migration of skin and lung fibroblasts from SSc patients and healthy controls. Normal lung but not skin fibroblasts consistently elongated and aligned with underlying collagen and migrated dependent on PDGF or serum. SSc lung fibroblasts remained growth factor dependent, did not migrate more rapidly and were less restricted to alignment of the collagen. Multiple collagen proline and lysine-modifying enzymes were identified in SSc but not control fibroblast extracellular matrix preparations, indicating differential levels of ECM modification by the diseased cells. Profiling of migrating cells revealed a possible SCF/c-Kit paracrine mechanism contributing to migration via a subpopulation of cells. Heparin, which binds ligands including PDGF and SCF, and imatininib which blocks downstream tyrosine kinase receptors, both inhibited lung fibroblast migration individually but showed synergy in SSc cells. Pathologic lung fibroblasts from SSc patients modify ECM during migration but remain growth factor dependent and sensitive to inhibitors.
format	article
author	Bahja Ahmed Abdi Henry Lopez Sarah Karrar Elisabetta Renzoni Athol Wells Angela Tam Oseme Etomi J. Justin Hsuan George R. Martin Xu Shiwen Christopher P. Denton David Abraham Richard Stratton
author_facet	Bahja Ahmed Abdi Henry Lopez Sarah Karrar Elisabetta Renzoni Athol Wells Angela Tam Oseme Etomi J. Justin Hsuan George R. Martin Xu Shiwen Christopher P. Denton David Abraham Richard Stratton
author_sort	Bahja Ahmed Abdi
title	Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration
title_short	Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration
title_full	Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration
title_fullStr	Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration
title_full_unstemmed	Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration
title_sort	use of patterned collagen coated slides to study normal and scleroderma lung fibroblast migration
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6d882f743d80403ea27006239ee20cc9
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Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration

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