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Increased deposition of glycosaminoglycans and altered structure of heparan sulfate in idiopathic pulmonary fibrosis

Westergren-Thorsson, Gunilla LU ; Hedström, Ulf LU ; Nybom, Annika LU ; Tykesson, Emil LU ; Åhrman, Emma LU ; Hornfelt, Marie LU ; Maccarana, Marco LU ; van Kuppevelt, Toin H; Dellgren, Göran and Wildt, Marie LU , et al. (2017) In International Journal of Biochemistry and Cell Biology 83. p.27-38
Abstract

Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant deposition of extracellular matrix (ECM) constituents, including glycosaminoglycans (GAGs), that may play a role in remodelling processes by influencing critical mediators such as growth factors. We hypothesize that GAGs may be altered in IPF and that this contribute to create a pro-fibrotic environment. The aim of this study was therefore to examine the fine structure of heparan sulfate (HS), chondroitin/dermatan sulfate (CS/DS) and hyaluronan (HA) in lung samples from IPF patients and from control subjects. GAGs in lung samples from severe IPF patients and donor lungs were analyzed with HPLC. HS was assessed by immunohistochemistry and collagen was quantified as... (More)

Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant deposition of extracellular matrix (ECM) constituents, including glycosaminoglycans (GAGs), that may play a role in remodelling processes by influencing critical mediators such as growth factors. We hypothesize that GAGs may be altered in IPF and that this contribute to create a pro-fibrotic environment. The aim of this study was therefore to examine the fine structure of heparan sulfate (HS), chondroitin/dermatan sulfate (CS/DS) and hyaluronan (HA) in lung samples from IPF patients and from control subjects. GAGs in lung samples from severe IPF patients and donor lungs were analyzed with HPLC. HS was assessed by immunohistochemistry and collagen was quantified as hydroxyproline content. The total amount of HS, CS/DS and HA was increased in IPF lungs but there was no significant difference in the total collagen content. We found a relative increase in total sulfation of HS due to increment of 2-O, 6-O and N-sulfation and a higher proportion of sulfation in CS/DS. Highly sulfated HS was located in the border zone between denser areas and more normal looking alveolar parenchyma in basement membranes of blood vessels and airways, that were immuno-positive for perlecan, as well as on the cell surface of spindle-shaped cells in the alveolar interstitium. These findings show for the first time that both the amount and structure of glycosaminoglycans are altered in IPF. These changes may contribute to the tissue remodelling in IPF by altering growth factor retention and activity, creating a pro-fibrotic ECM landscape.

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International Journal of Biochemistry and Cell Biology
volume
83
pages
12 pages
publisher
Elsevier
external identifiers
  • scopus:85006298195
  • wos:000394192400003
ISSN
1878-5875
DOI
10.1016/j.biocel.2016.12.005
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English
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yes
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dfa7f9c5-7a23-4f0e-bead-e0a81c0a7e29
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2017-01-03 10:02:20
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2018-04-08 04:52:31
@article{dfa7f9c5-7a23-4f0e-bead-e0a81c0a7e29,
  abstract     = {<p>Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant deposition of extracellular matrix (ECM) constituents, including glycosaminoglycans (GAGs), that may play a role in remodelling processes by influencing critical mediators such as growth factors. We hypothesize that GAGs may be altered in IPF and that this contribute to create a pro-fibrotic environment. The aim of this study was therefore to examine the fine structure of heparan sulfate (HS), chondroitin/dermatan sulfate (CS/DS) and hyaluronan (HA) in lung samples from IPF patients and from control subjects. GAGs in lung samples from severe IPF patients and donor lungs were analyzed with HPLC. HS was assessed by immunohistochemistry and collagen was quantified as hydroxyproline content. The total amount of HS, CS/DS and HA was increased in IPF lungs but there was no significant difference in the total collagen content. We found a relative increase in total sulfation of HS due to increment of 2-O, 6-O and N-sulfation and a higher proportion of sulfation in CS/DS. Highly sulfated HS was located in the border zone between denser areas and more normal looking alveolar parenchyma in basement membranes of blood vessels and airways, that were immuno-positive for perlecan, as well as on the cell surface of spindle-shaped cells in the alveolar interstitium. These findings show for the first time that both the amount and structure of glycosaminoglycans are altered in IPF. These changes may contribute to the tissue remodelling in IPF by altering growth factor retention and activity, creating a pro-fibrotic ECM landscape.</p>},
  author       = {Westergren-Thorsson, Gunilla and Hedström, Ulf and Nybom, Annika and Tykesson, Emil and Åhrman, Emma and Hornfelt, Marie and Maccarana, Marco and van Kuppevelt, Toin H and Dellgren, Göran and Wildt, Marie and Zhou, Xiao-Hong and Eriksson, Leif and Bjermer, Leif and Hallgren, Oskar},
  issn         = {1878-5875},
  language     = {eng},
  pages        = {27--38},
  publisher    = {Elsevier},
  series       = {International Journal of Biochemistry and Cell Biology},
  title        = {Increased deposition of glycosaminoglycans and altered structure of heparan sulfate in idiopathic pulmonary fibrosis},
  url          = {http://dx.doi.org/10.1016/j.biocel.2016.12.005},
  volume       = {83},
  year         = {2017},
}