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

Title: Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration
Authors: Abdi, BA
Lopez, H
Karrar, S
Renzoni, E
Wells, A
Tam, A
Etomi, O
Hsuan, JJ
Martin, GR
Xu, S
Denton, CP
Abraham, D
Stratton, R
Item Type: Journal Article
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/cKit 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.
Issue Date: 1-Jun-2017
Date of Acceptance: 13-Apr-2017
URI: http://hdl.handle.net/10044/1/54008
DOI: https://dx.doi.org/10.1038/s41598-017-02621-3
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 7
Copyright Statement: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2017
Sponsor/Funder: Arthritis Research UK
British Lung Foundation
Raynaud's and Scleroderma Association
Funder's Grant Number: 20719
RG14-10
BR11
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
IDIOPATHIC PULMONARY-FIBROSIS
PLACEBO-CONTROLLED TRIAL
STEM-CELL FACTOR
SYSTEMIC-SCLEROSIS
GROWTH-FACTOR
DOUBLE-BLIND
DISEASE-MECHANISMS
IMATINIB MESYLATE
MAST-CELLS
SKIN
Publication Status: Published
Article Number: 2628
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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