Nemani, Sai Sneha Priya; Vermeulen, Cornelis Joseph; Pech, Martin; Faiz, Alen; Oliver, Brian George G; van den Berge, Maarten; Burgess, Janette Kay; Kopp, Matthias V.; Weckmann, Markus (2021). COL4A3 expression in asthmatic epithelium depends on intronic methylation and ZNF263 binding. ERJ Open Research, 7(2) European Respiratory Society 10.1183/23120541.00802-2020
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Background
Reduction of COL4A3, one of the six isoforms of collagen 4, in asthmatic airways results in increased inflammation and angiogenesis, implicating it as a central part of asthma pathogenesis. However, to date, the path underlying these diminished COL4A3 levels has been elusive. This study investigated a possible mechanism underlying the reduction of COL4A3 expression.
Methods
Bronchial biopsies of 76 patients with asthma and 83 controls were subjected to RNA-sequencing and DNA methylation bead arrays to identify expression and methylation changes. The binding of ZNF263 was analysed by chromatin-immunoprecipitation sequencing coupled with quantitative (q)PCR. Effects of ZNF263 silencing, using small interfering RNA, on the COL4A3 expression were studied using qPCR.
Results
COL4A3 expression was significantly reduced in bronchial biopsies compared to healthy controls, whereas DNA methylation levels at cg11797365 were increased. COL4A3 expression levels were significantly low in asthmatics without inhaled corticosteroid (ICS) use, whereas the expression was not statistically different between asthmatics using ICS and controls. Methylation levels at cg11797365 in vitro were increased upon consecutive rhinovirus infections.
Conclusion
Our data indicate an epigenetic modification as a contributing factor for the loss of COL4A3 expression in asthmatic airway epithelium.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine 04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Paediatric Pneumology |
UniBE Contributor: |
Kopp, Matthias Volkmar |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2312-0541 |
Publisher: |
European Respiratory Society |
Language: |
English |
Submitter: |
Anette van Dorland |
Date Deposited: |
23 Aug 2021 15:56 |
Last Modified: |
05 Dec 2022 15:52 |
Publisher DOI: |
10.1183/23120541.00802-2020 |
PubMed ID: |
34109240 |
BORIS DOI: |
10.48350/157925 |
URI: |
https://boris.unibe.ch/id/eprint/157925 |
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