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Absence of fibromodulin affects matrix composition, collagen deposition and cell turnover in healthy and fibrotic lung parenchyma.

Rydell-Törmänen, Kristina LU ; Andréasson, Kristofer LU ; Hesselstrand, Roger LU and Westergren-Thorsson, Gunilla LU (2014) In Scientific Reports 4.
Abstract
The ECM exerts great effects on cells, and changed composition may therefore have profound impact. Small leucine-rich proteoglycans, e.g. fibromodulin, are essential in collagen assembly. Our aim was to investigate the role of fibromodulin in healthy and fibrotic lung parenchyma, theorizing that fibromodulin-deficient animals would be protected against fibrosis. Repeated subcutaneous bleomycin-injections were given to wild type and fibromodulin-deficient mice, inducing pulmonary fibrosis. Development of fibrosis, ECM composition, cell turnover and inflammatory responses were investigated. Fibromodulin-deficient animals were not protected from fibrosis, but the composition of the matrix was affected, with decreased Collagen I in... (More)
The ECM exerts great effects on cells, and changed composition may therefore have profound impact. Small leucine-rich proteoglycans, e.g. fibromodulin, are essential in collagen assembly. Our aim was to investigate the role of fibromodulin in healthy and fibrotic lung parenchyma, theorizing that fibromodulin-deficient animals would be protected against fibrosis. Repeated subcutaneous bleomycin-injections were given to wild type and fibromodulin-deficient mice, inducing pulmonary fibrosis. Development of fibrosis, ECM composition, cell turnover and inflammatory responses were investigated. Fibromodulin-deficient animals were not protected from fibrosis, but the composition of the matrix was affected, with decreased Collagen I in fibromodulin-deficient animals, both in controls (0.07 ± 0.04% vs. 0.18 ± 0.07% tissue area) and after bleomycin (0.37 ± 0.16% vs. 0.61 ± 0.21% tissue area). Biglycan was increased in fibromodulin-deficient animals, whereas decorin was decreased. Furthermore, bleomycin increased cell turnover in wild type, but only proliferation in fibromodulin-deficient animals, resulting in hyperplasia. In addition, the bleomycin-induced immune response was affected in fibromodulin-deficient animals. We thus conclude that fibromodulin has a profound effect on ECM, both in healthy and fibrotic lung parenchyma, and may be providing a permissive microenvironment affecting cell turnover. Furthermore, this study highlights the need to acknowledge specific ECM components, when assessing tissue properties and ultimately cell behaviour. (Less)
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organization
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Contribution to journal
publication status
published
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in
Scientific Reports
volume
4
publisher
Nature Publishing Group
external identifiers
  • pmid:25230586
  • wos:000341941800001
  • scopus:84923356628
ISSN
2045-2322
DOI
10.1038/srep06383
language
English
LU publication?
yes
id
c4a16a13-abb8-48de-b1d7-a7331645e4fc (old id 4691360)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25230586?dopt=Abstract
date added to LUP
2014-10-07 19:36:06
date last changed
2017-10-22 04:25:15
@article{c4a16a13-abb8-48de-b1d7-a7331645e4fc,
  abstract     = {The ECM exerts great effects on cells, and changed composition may therefore have profound impact. Small leucine-rich proteoglycans, e.g. fibromodulin, are essential in collagen assembly. Our aim was to investigate the role of fibromodulin in healthy and fibrotic lung parenchyma, theorizing that fibromodulin-deficient animals would be protected against fibrosis. Repeated subcutaneous bleomycin-injections were given to wild type and fibromodulin-deficient mice, inducing pulmonary fibrosis. Development of fibrosis, ECM composition, cell turnover and inflammatory responses were investigated. Fibromodulin-deficient animals were not protected from fibrosis, but the composition of the matrix was affected, with decreased Collagen I in fibromodulin-deficient animals, both in controls (0.07 ± 0.04% vs. 0.18 ± 0.07% tissue area) and after bleomycin (0.37 ± 0.16% vs. 0.61 ± 0.21% tissue area). Biglycan was increased in fibromodulin-deficient animals, whereas decorin was decreased. Furthermore, bleomycin increased cell turnover in wild type, but only proliferation in fibromodulin-deficient animals, resulting in hyperplasia. In addition, the bleomycin-induced immune response was affected in fibromodulin-deficient animals. We thus conclude that fibromodulin has a profound effect on ECM, both in healthy and fibrotic lung parenchyma, and may be providing a permissive microenvironment affecting cell turnover. Furthermore, this study highlights the need to acknowledge specific ECM components, when assessing tissue properties and ultimately cell behaviour.},
  articleno    = {6383},
  author       = {Rydell-Törmänen, Kristina and Andréasson, Kristofer and Hesselstrand, Roger and Westergren-Thorsson, Gunilla},
  issn         = {2045-2322},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Absence of fibromodulin affects matrix composition, collagen deposition and cell turnover in healthy and fibrotic lung parenchyma.},
  url          = {http://dx.doi.org/10.1038/srep06383},
  volume       = {4},
  year         = {2014},
}