Expression, activity and localization of lysosomal sulfatases in Chronic Obstructive Pulmonary Disease
| Autor: | Dalja Helihel, Gunilla Westergren-Thorsson, Prajakta Jogdand, Leif Bjermer, Julie Weidner, Ellen Tufvesson, Linnea Jarenbäck, Ida Åberg, Jaro Ankerst, Jonas S. Erjefält |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Hydrolases lcsh:Medicine Disease Immunofluorescence Article Extracellular matrix Pathogenesis Pulmonary Disease Chronic Obstructive 03 medical and health sciences 0302 clinical medicine medicine Humans Oxidoreductases Acting on Sulfur Group Donors RNA Messenger lcsh:Science Lung Glycoproteins Messenger RNA COPD Smokers Multidisciplinary medicine.diagnostic_test business.industry lcsh:R medicine.disease Chondroitinsulfatases respiratory tract diseases 030104 developmental biology medicine.anatomical_structure Cancer research Immunohistochemistry Female lcsh:Q Sulfatases business 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|