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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2017-06-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-017-02621-3 |
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doaj-6d882f743d80403ea27006239ee20cc92020-12-08T00:17:57ZengNature Publishing GroupScientific Reports2045-23222017-06-017111110.1038/s41598-017-02621-3Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast MigrationBahja Ahmed Abdi0Henry Lopez1Sarah Karrar2Elisabetta Renzoni3Athol Wells4Angela Tam5Oseme Etomi6J. Justin Hsuan7George R. Martin8Xu Shiwen9Christopher P. Denton10David Abraham11Richard Stratton12Centre for Rheumatology and Connective Tissue Disease, Royal Free Hospital Campus, University College Medical SchoolMuriGenics, Inc.Centre for Rheumatology and Connective Tissue Disease, Royal Free Hospital Campus, University College Medical SchoolImperial College London, Royal Brompton CampusImperial College London, Royal Brompton CampusCentre for Rheumatology and Connective Tissue Disease, Royal Free Hospital Campus, University College Medical SchoolCentre for Rheumatology and Connective Tissue Disease, Royal Free Hospital Campus, University College Medical SchoolInstitute for Liver and Digestive Health, Royal Free Hospital Campus, University College Medical School Rowland Hill StreetMuriGenics, Inc.Centre for Rheumatology and Connective Tissue Disease, Royal Free Hospital Campus, University College Medical SchoolCentre for Rheumatology and Connective Tissue Disease, Royal Free Hospital Campus, University College Medical SchoolCentre for Rheumatology and Connective Tissue Disease, Royal Free Hospital Campus, University College Medical SchoolCentre for Rheumatology and Connective Tissue Disease, Royal Free Hospital Campus, University College Medical SchoolAbstract 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.https://doi.org/10.1038/s41598-017-02621-3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-06-01 |
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. |
url |
https://doi.org/10.1038/s41598-017-02621-3 |
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