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Expression, activity and localization of lysosomal sulfatases in Chronic Obstructive Pulmonary Disease

Weidner, Julie LU ; Jogdand, Prajakta LU ; Jarenbäck, Linnea LU ; Åberg, Ida LU ; Helihel, Dalja ; Ankerst, Jaro LU orcid ; Westergren-Thorsson, Gunilla LU orcid ; Bjermer, Leif LU ; Erjefält, Jonas S. LU and Tufvesson, Ellen LU (2019) In Scientific Reports 9(1).
Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of death world-wide. Recently, we showed that COPD is associated with gene polymorphisms in SUMF1, a master regulator of sulfatases. Sulfatases are involved in extracellular matrix remodeling and activated by SUMF1, but their role in the lung is poorly described. We aimed to examine how sulfatases are affected in the airways of patients with COPD compared to ever smokers and never smokers. We observed that mRNA expression of the sulfatases GALNS, GNS and IDS was increased, while protein expression of many sulfatases was decreased in COPD fibroblasts. Several sulfatases, including GALNS, IDS, and SGSH, showed increased activity in COPD fibroblasts. Examination of different... (More)

Chronic obstructive pulmonary disease (COPD) is a leading cause of death world-wide. Recently, we showed that COPD is associated with gene polymorphisms in SUMF1, a master regulator of sulfatases. Sulfatases are involved in extracellular matrix remodeling and activated by SUMF1, but their role in the lung is poorly described. We aimed to examine how sulfatases are affected in the airways of patients with COPD compared to ever smokers and never smokers. We observed that mRNA expression of the sulfatases GALNS, GNS and IDS was increased, while protein expression of many sulfatases was decreased in COPD fibroblasts. Several sulfatases, including GALNS, IDS, and SGSH, showed increased activity in COPD fibroblasts. Examination of different sulfatases by immunofluorescence showed that IDS, ARSB, GNS and SGSH in fibroblasts were localized to sites other than their reported destination. Using a master panel from different organs, RNA expression of all sulfatases could be observed in lung tissue. Additionally, immunohistochemistry on lung biopsies indicated differing expression of sulfatases in COPD patients. In conclusion, mRNA, protein expression, sulfatase activity levels, and localization of sulfatases are altered in lung fibroblasts and lung tissue from COPD patients and may be mechanistically important in COPD pathogenesis. This could contribute to the understanding of the disease mechanism in COPD and in the long run, to lead to more individualized therapies.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
9
issue
1
article number
1991
publisher
Nature Publishing Group
external identifiers
  • pmid:30760748
  • scopus:85061475433
ISSN
2045-2322
DOI
10.1038/s41598-018-37958-w
language
English
LU publication?
yes
id
bbfafd71-5985-4db9-8530-b4ec384a7d69
date added to LUP
2019-02-21 07:34:17
date last changed
2025-01-09 02:59:00
@article{bbfafd71-5985-4db9-8530-b4ec384a7d69,
  abstract     = {{<p>Chronic obstructive pulmonary disease (COPD) is a leading cause of death world-wide. Recently, we showed that COPD is associated with gene polymorphisms in SUMF1, a master regulator of sulfatases. Sulfatases are involved in extracellular matrix remodeling and activated by SUMF1, but their role in the lung is poorly described. We aimed to examine how sulfatases are affected in the airways of patients with COPD compared to ever smokers and never smokers. We observed that mRNA expression of the sulfatases GALNS, GNS and IDS was increased, while protein expression of many sulfatases was decreased in COPD fibroblasts. Several sulfatases, including GALNS, IDS, and SGSH, showed increased activity in COPD fibroblasts. Examination of different sulfatases by immunofluorescence showed that IDS, ARSB, GNS and SGSH in fibroblasts were localized to sites other than their reported destination. Using a master panel from different organs, RNA expression of all sulfatases could be observed in lung tissue. Additionally, immunohistochemistry on lung biopsies indicated differing expression of sulfatases in COPD patients. In conclusion, mRNA, protein expression, sulfatase activity levels, and localization of sulfatases are altered in lung fibroblasts and lung tissue from COPD patients and may be mechanistically important in COPD pathogenesis. This could contribute to the understanding of the disease mechanism in COPD and in the long run, to lead to more individualized therapies.</p>}},
  author       = {{Weidner, Julie and Jogdand, Prajakta and Jarenbäck, Linnea and Åberg, Ida and Helihel, Dalja and Ankerst, Jaro and Westergren-Thorsson, Gunilla and Bjermer, Leif and Erjefält, Jonas S. and Tufvesson, Ellen}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Expression, activity and localization of lysosomal sulfatases in Chronic Obstructive Pulmonary Disease}},
  url          = {{http://dx.doi.org/10.1038/s41598-018-37958-w}},
  doi          = {{10.1038/s41598-018-37958-w}},
  volume       = {{9}},
  year         = {{2019}},
}