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Asporin-deficient mice have tougher skin and altered skin glycosaminoglycan content and structure

Maccarana, Marco LU ; Svensson, René B. LU ; Knutsson, Anki LU ; Giannopoulos, Antonis; Pelkonen, Mea LU ; Weis, Mary Ann; Eyre, David R; Warman, Matthew and Kalamajski, Sebastian (2017) In PLoS ONE 12(8).
Abstract

The main structural component of connective tissues is fibrillar, cross-linked collagen whose fibrillogenesis can be modulated by Small Leucine-Rich Proteins/Proteoglycans (SLRPs). Not all SLRPs’ effects on collagen and extracellular matrix in vivo have been elucidated; one of the less investigated SLRPs is asporin. Here we describe the successful generation of an Aspn-/- mouse model and the investigation of the Aspn-/- skin phenotype. Functionally, Aspn-/- mice had an increased skin mechanical toughness, although there were no structural changes present on histology or immunohistochemistry. Electron microscopy analyses showed 7% thinner collagen fibrils in Aspn-/- mice (not statistically... (More)

The main structural component of connective tissues is fibrillar, cross-linked collagen whose fibrillogenesis can be modulated by Small Leucine-Rich Proteins/Proteoglycans (SLRPs). Not all SLRPs’ effects on collagen and extracellular matrix in vivo have been elucidated; one of the less investigated SLRPs is asporin. Here we describe the successful generation of an Aspn-/- mouse model and the investigation of the Aspn-/- skin phenotype. Functionally, Aspn-/- mice had an increased skin mechanical toughness, although there were no structural changes present on histology or immunohistochemistry. Electron microscopy analyses showed 7% thinner collagen fibrils in Aspn-/- mice (not statistically significant). Several matrix genes were upregulated, including collagens (Col1a1, Col1a2, Col3a1), matrix metalloproteinases (Mmp2, Mmp3) and lysyl oxidases (Lox, Loxl2), while lysyl hydroxylase (Plod2) was downregulated. Intriguingly no differences were observed in collagen protein content or in collagen cross-linking-related lysine oxidation or hydroxylation. The glycosaminoglycan content and structure in Aspn-/- skin was profoundly altered: chondroitin/dermatan sulfate was more than doubled and had an altered composition, while heparan sulfate was halved and had a decreased sulfation. Also, decorin and biglycan were doubled in Aspn-/- skin. Overall, asporin deficiency changes skin glycosaminoglycan composition, and decorin and biglycan content, which may explain the changes in skin mechanical properties.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Asporin-deficient, mice, skin, glycosaminoglycan
in
PLoS ONE
volume
12
issue
8
publisher
Public Library of Science
external identifiers
  • scopus:85028875312
  • pmid:28859141
  • wos:000408740500060
ISSN
1932-6203
DOI
10.1371/journal.pone.0184028
language
English
LU publication?
yes
id
c8133688-d0a0-492a-8623-d60283a792e2
date added to LUP
2017-10-10 12:11:29
date last changed
2018-01-16 13:22:33
@article{c8133688-d0a0-492a-8623-d60283a792e2,
  abstract     = {<p>The main structural component of connective tissues is fibrillar, cross-linked collagen whose fibrillogenesis can be modulated by Small Leucine-Rich Proteins/Proteoglycans (SLRPs). Not all SLRPs’ effects on collagen and extracellular matrix in vivo have been elucidated; one of the less investigated SLRPs is asporin. Here we describe the successful generation of an Aspn<sup>-/-</sup> mouse model and the investigation of the Aspn<sup>-/-</sup> skin phenotype. Functionally, Aspn<sup>-/-</sup> mice had an increased skin mechanical toughness, although there were no structural changes present on histology or immunohistochemistry. Electron microscopy analyses showed 7% thinner collagen fibrils in Aspn<sup>-/-</sup> mice (not statistically significant). Several matrix genes were upregulated, including collagens (Col1a1, Col1a2, Col3a1), matrix metalloproteinases (Mmp2, Mmp3) and lysyl oxidases (Lox, Loxl2), while lysyl hydroxylase (Plod2) was downregulated. Intriguingly no differences were observed in collagen protein content or in collagen cross-linking-related lysine oxidation or hydroxylation. The glycosaminoglycan content and structure in Aspn<sup>-/-</sup> skin was profoundly altered: chondroitin/dermatan sulfate was more than doubled and had an altered composition, while heparan sulfate was halved and had a decreased sulfation. Also, decorin and biglycan were doubled in Aspn<sup>-/-</sup> skin. Overall, asporin deficiency changes skin glycosaminoglycan composition, and decorin and biglycan content, which may explain the changes in skin mechanical properties.</p>},
  articleno    = {e0184028},
  author       = {Maccarana, Marco and Svensson, René B. and Knutsson, Anki and Giannopoulos, Antonis and Pelkonen, Mea and Weis, Mary Ann and Eyre, David R and Warman, Matthew and Kalamajski, Sebastian},
  issn         = {1932-6203},
  keyword      = {Asporin-deficient,mice,skin,glycosaminoglycan},
  language     = {eng},
  month        = {08},
  number       = {8},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Asporin-deficient mice have tougher skin and altered skin glycosaminoglycan content and structure},
  url          = {http://dx.doi.org/10.1371/journal.pone.0184028},
  volume       = {12},
  year         = {2017},
}