Disentangling the multifactorial contributions of fibronectin, collagen and cyclic strain on MMP expression and extracellular matrix remodeling by fibroblasts

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Author(s) Zhang, Yang, Lin, Zhe, Foolen, Jasper, Schoen, Ingmar, Santoro, Alberto, Zenobi-Wong, Marcy, Vogel, Viola
Publication Type Journal Items, Publication Status: Published
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Title Disentangling the multifactorial contributions of fibronectin, collagen and cyclic strain on MMP expression and extracellular matrix remodeling by fibroblasts
Author(s) Zhang, Yang
Lin, Zhe
Foolen, Jasper
Schoen, Ingmar
Santoro, Alberto
Zenobi-Wong, Marcy
Vogel, Viola
Journal or Series Title Matrix Biology
Volume Number 40
Start Page 62
End Page 72
ISSN 0945-053X
1569-1802
Publisher Elsevier
Publication Place Oxford
Publication Date 2014-11
Keyword(s) Mechanobiology
Human foreskin fibroblasts
Cyclic stretching
Matrix metalloproteinases
FRET-based molecular tension sensors
Abstract Early wound healing is associated with fibroblasts assembling a provisional fibronectin-rich extracellular matrix (ECM), which is subsequently remodeled and interlaced by type I collagen. This exposes fibroblasts to time-variant sets of matrices during different stages of wound healing. Our goal was thus to gain insight into the ECM-driven functional regulation of human foreskin fibroblasts (HFFs) being either anchored to a fibronectin (Fn) or to a collagen-decorated matrix, in the absence or presence of cyclic mechanical strain. While the cells reoriented in response to the onset of uniaxial cyclic strain, cells assembled exogenously added Fn with a preferential Fn-fiber alignment along their new orientation. Exposure of HFFs to exogenous Fn resulted in an increase in matrix metalloproteinase (MMP) expression levels, i.e. MMP-15 (RT-qPCR), and MMP-9 activity (zymography), while subsequent exposure to collagen slightly reduced MMP-15 expression and MMP-9 activity compared to Fn-exposure alone. Cyclic strain upregulated Fn fibrillogenesis and actin stress fiber formation, but had comparatively little effect on MMP activity. We thus propose that the appearance of collagen might start to steer HFFs towards homeostasis, as it decreased both MMP secretion and the tension of Fn matrix fibrils as assessed by Fluorescence Resonance Energy Transfer. These results suggest that HFFs might have a high ECM remodeling or repair capacity in contact with Fn alone (early event), which is reduced in the presence of Col1 (later event), thereby down-tuning HFF activity, a processes which would be required in a tissue repair process to finally reach tissue homeostasis.
DOI 10.1016/j.matbio.2014.09.001
Additional Notes Received 5 July 2014, Revised 3 September 2014, Accepted 4 September 2014, Published online 11 September 2014
Document Type Article
Publication Status Published
Language English
Assigned Organisational Unit(s) 03949
03640
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NEBIS System Number 000938729
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SCOPUS-84918581674
WOS-000347597700009
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@article{Zhng2014,
  author = "Zhang, Yang and Lin, Zhe and Foolen, Jasper and Schoen, Ingmar and Santoro, Alberto and Zenobi-Wong, Marcy and Vogel, Viola",
  title = "{D}isentangling the multifactorial contributions of fibronectin, collagen and cyclic strain on {M}{M}{P} expression and extracellular matrix remodeling by fibroblasts",
  journal = "Matrix Biology",
  year = 2014,
  volume = "40",
  pages = "62--72",
  month = nov,
}


E-Citations record created: Fri, 19 Sep 2014, 13:26:08 CET