Modulation of pulmonary desmosomes by inhaler therapy in preterm-born children with bronchopulmonary dysplasia.

Autor: Course CW; Department of Child Health, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK., Lewis PA; Proteomics Facility, Faculty of Life Sciences, University of Bristol, Bristol, UK., Kotecha SJ; Department of Child Health, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK., Cousins M; Department of Child Health, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK.; Department of Paediatrics, Cardiff and Vale University Health Board, Cardiff, UK., Hart K; Department of Paediatrics, Cardiff and Vale University Health Board, Cardiff, UK., Watkins WJ; Department of Child Health, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK., Heesom KJ; Proteomics Facility, Faculty of Life Sciences, University of Bristol, Bristol, UK., Kotecha S; Department of Child Health, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK. kotechas@cardiff.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 May 05; Vol. 13 (1), pp. 7330. Date of Electronic Publication: 2023 May 05.
DOI: 10.1038/s41598-023-34233-5
Abstrakt: Despite evidence demonstrating persistent lung function deficits in preterm-born children, especially in those who had bronchopulmonary dysplasia (BPD) in infancy, the underlying biological mechanisms explaining these lung function deficits remain poorly understood. We characterised the exhaled breath condensate (EBC) proteome in preterm-born children, with and without BPD; and before and after inhaler treatment. EBC from children aged 7-12 years, from the Respiratory Health Outcomes in Neonates (RHiNO) study, were analysed by Nano-LC Mass Spectrometry with Tandem Mass Tag labelling. Children with percent predicted forced expiratory volume in 1 second ≤ 85% were enrolled to a 12-week blinded randomised trial of inhaled corticosteroids alone (ICS) or with long-acting β 2 -agonist (ICS/LABA) or placebo. EBC was analysed from 218 children at baseline, and 46 children received randomised inhaled therapy. 210 proteins were detected in total. For the 19 proteins present in every sample, the desmosome proteins: desmoglein-1, desmocollin-1 and plakoglobin were significantly decreased, and cytokeratin-6A was increased in preterm-born children with BPD when compared to preterm- and term-born controls. ICS/LABA treatment significantly increased abundance of desmoglein-1, desmocollin-1 and plakoglobin in the BPD group with low lung function, and significantly increased plakoglobin in those without BPD. No differences were noted after ICS treatment. Exploratory analyses of proteins not detected in all samples suggested decreased abundance of several antiproteases. This study provides proteomic evidence of ongoing pulmonary structural changes with decreased desmosomes in school-aged preterm-born children with BPD and low lung function, which was reversed with combined inhaled corticosteroids and long-acting β 2 -agonists therapy.
(© 2023. The Author(s).)
Databáze: MEDLINE
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