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Change in the chondroitin/dermatan structure in distal lung tissue from COPD patients

Alsafadi, Hani N LU orcid ; Nybom, Annika LU ; Wagner, Darcy LU orcid ; Malmström, Anders LU orcid ; Lindstedt, Sandra LU ; Bjermer, Leif LU ; Dellgren, Göran ; Malmström, Johan LU orcid ; Tykesson, Emil LU orcid and Westergren-Thorsson, Gunilla LU orcid , et al. (2026) In Scientific Reports 16. p.1-14
Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by airway remodeling, including emphysema and fibrosis. Proteoglycans and their glycosaminoglycan (GAG) chains are key components of the extracellular matrix and may be altered as the disease advances. This study analyzed lung tissue from COPD patients (GOLD stages II-III and IV), non-COPD smokers, and non-smokers to assess proteoglycan and GAG changes. While LC-MS revealed no alterations in chondroitin/dermatan sulfate (CS/DS) or heparan sulfate (HS) proteoglycan core proteins, the total GAG level increased in GOLD II-IV patients. HS displayed increased N- and 2-O-sulfation in GOLD IV, while CS/DS levels and 4-O-sulfation were enhanced across GOLD... (More)

Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by airway remodeling, including emphysema and fibrosis. Proteoglycans and their glycosaminoglycan (GAG) chains are key components of the extracellular matrix and may be altered as the disease advances. This study analyzed lung tissue from COPD patients (GOLD stages II-III and IV), non-COPD smokers, and non-smokers to assess proteoglycan and GAG changes. While LC-MS revealed no alterations in chondroitin/dermatan sulfate (CS/DS) or heparan sulfate (HS) proteoglycan core proteins, the total GAG level increased in GOLD II-IV patients. HS displayed increased N- and 2-O-sulfation in GOLD IV, while CS/DS levels and 4-O-sulfation were enhanced across GOLD II-IV. These findings were supported by transcriptomic data indicating upregulation of CHST11, the main CS/DS 4-O-sulfotransferase. In line with previous findings, TGF-β signaling was shown to be enriched in COPD patients and to regulate the CHST11 expression. These results were confirmed by TGF-β stimulation of lung fibroblasts showing increased CS/DS levels, 4-O-sulfation, and CHST11 expression. In conclusion, COPD is associated with disease-stage-specific changes in GAG sulfation, particularly enhanced CS/DS 4-O-sulfation that is likely to be driven by TGF-β. These alterations may contribute to extracellular matrix remodeling and represent potential targets for therapeutic intervention to mitigate disease progression.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Pulmonary Disease, Chronic Obstructive/metabolism, Lung/metabolism, Male, Female, Dermatan Sulfate/metabolism, Middle Aged, Aged, Sulfotransferases/metabolism, Chondroitin/metabolism, Transforming Growth Factor beta/metabolism, Glycosaminoglycans/metabolism, Chondroitin Sulfates/metabolism, Fibroblasts/metabolism
in
Scientific Reports
volume
16
article number
9721
pages
1 - 14
publisher
Nature Publishing Group
external identifiers
  • scopus:105033544149
  • pmid:41872350
ISSN
2045-2322
DOI
10.1038/s41598-026-44120-4
language
English
LU publication?
yes
additional info
© 2026. The Author(s).
id
bf4cae25-5b98-4048-a64e-94f76ead1b97
date added to LUP
2026-03-26 08:31:17
date last changed
2026-05-29 05:55:38
@article{bf4cae25-5b98-4048-a64e-94f76ead1b97,
  abstract     = {{<p>Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by airway remodeling, including emphysema and fibrosis. Proteoglycans and their glycosaminoglycan (GAG) chains are key components of the extracellular matrix and may be altered as the disease advances. This study analyzed lung tissue from COPD patients (GOLD stages II-III and IV), non-COPD smokers, and non-smokers to assess proteoglycan and GAG changes. While LC-MS revealed no alterations in chondroitin/dermatan sulfate (CS/DS) or heparan sulfate (HS) proteoglycan core proteins, the total GAG level increased in GOLD II-IV patients. HS displayed increased N- and 2-O-sulfation in GOLD IV, while CS/DS levels and 4-O-sulfation were enhanced across GOLD II-IV. These findings were supported by transcriptomic data indicating upregulation of CHST11, the main CS/DS 4-O-sulfotransferase. In line with previous findings, TGF-β signaling was shown to be enriched in COPD patients and to regulate the CHST11 expression. These results were confirmed by TGF-β stimulation of lung fibroblasts showing increased CS/DS levels, 4-O-sulfation, and CHST11 expression. In conclusion, COPD is associated with disease-stage-specific changes in GAG sulfation, particularly enhanced CS/DS 4-O-sulfation that is likely to be driven by TGF-β. These alterations may contribute to extracellular matrix remodeling and represent potential targets for therapeutic intervention to mitigate disease progression.</p>}},
  author       = {{Alsafadi, Hani N and Nybom, Annika and Wagner, Darcy and Malmström, Anders and Lindstedt, Sandra and Bjermer, Leif and Dellgren, Göran and Malmström, Johan and Tykesson, Emil and Westergren-Thorsson, Gunilla and Hallgren, Oskar}},
  issn         = {{2045-2322}},
  keywords     = {{Humans; Pulmonary Disease, Chronic Obstructive/metabolism; Lung/metabolism; Male; Female; Dermatan Sulfate/metabolism; Middle Aged; Aged; Sulfotransferases/metabolism; Chondroitin/metabolism; Transforming Growth Factor beta/metabolism; Glycosaminoglycans/metabolism; Chondroitin Sulfates/metabolism; Fibroblasts/metabolism}},
  language     = {{eng}},
  month        = {{03}},
  pages        = {{1--14}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Change in the chondroitin/dermatan structure in distal lung tissue from COPD patients}},
  url          = {{http://dx.doi.org/10.1038/s41598-026-44120-4}},
  doi          = {{10.1038/s41598-026-44120-4}},
  volume       = {{16}},
  year         = {{2026}},
}