Gene expression analysis of bronchial epithelium in adults with a history of bronchopulmonary dysplasia (BPD) compared to relevant control groups

<bold>Background/Aim:</bold> Premature birth and BPD are risk factors for respiratory diseases in adulthood. In the LUNAPRE cohort (<ext-link>NCT02923648</ext-link>), we´ve previously shown that adults with a BPD history were more obstructive than preterm individuals without BPD, full-term born mild intermittent asthmatics, and healthy term-born. Here, our aim is to explore gene expression changes in bronchial brushings (BB) to understand the cellular mechanisms. <bold>Methods:</bold> RNA-seq analysis was performed on BB samples from the LUNAPRE cohort. Gene expression data were explored using DESeq2 and pathway analysis. Healthy term-borns were used as a control group. <bold>Results:</bold> The list of differentially expressed genes (DEGs) in the asthma group revealed up-regulated markers of T2 inflammation, such as Periostin and Cystatin SN, not observed in BPD. The BPD group showed a small number of DEGs, including downregulation of TMEM270, METTL27, and CLDN4. These genes are located on chromosome 7 upstream of Elastin (ELN), a gene with complex transcriptional regulation. The non-BPD preterm group revealed no DEGs. <bold>Conclusions:</bold> BPD lung function impairment did not translate into major modifications in BB gene expression compared to healthy term-born. However, some differences were found in a few genes potentially related to the regulation of ELN, an important protein for lung elasticity. We will further investigate this point, combining clinical and other experimental cohort data. Critical genes related to T2 asthma were not dysregulated in BPD, providing crucial insights into potential therapeutic interventions. Prematurity on its own doesn´t impact gene expression in bronchial epithelium.

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Published
2024-09-14
DOI
https://doi.org/10.1183/13993003.congress-2024.pa2649
Primary Topic
Neonatal Respiratory Health Research
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article
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article

Gene expression analysis of bronchial epithelium in adults with a history of bronchopulmonary dysplasia (BPD) compared to relevant control groups

Åsa M. Wheelock, Iryna Kolosenko, Eva Berggren-Broström, Petra Um‐Bergström et al.
Neonatal Respiratory Health Research
article

Gene expression analysis of bronchial epithelium in adults with a history of bronchopulmonary dysplasia (BPD) compared to relevant control groups

Åsa M. Wheelock, Iryna Kolosenko, Eva Berggren-Broström, Petra Um‐Bergström, Klementy Shchetynsky, Martina Bonatti, Magnus Sköld
article en

Abstract

<bold>Background/Aim:</bold> Premature birth and BPD are risk factors for respiratory diseases in adulthood. In the LUNAPRE cohort (<ext-link>NCT02923648</ext-link>), we´ve previously shown that adults with a BPD history were more obstructive than preterm individuals without BPD, full-term born mild intermittent asthmatics, and healthy term-born. Here, our aim is to explore gene expression changes in bronchial brushings (BB) to understand the cellular mechanisms. <bold>Methods:</bold> RNA-seq analysis was performed on BB samples from the LUNAPRE cohort. Gene expression data were explored using DESeq2 and pathway analysis. Healthy term-borns were used as a control group. <bold>Results:</bold> The list of differentially expressed genes (DEGs) in the asthma group revealed up-regulated markers of T2 inflammation, such as Periostin and Cystatin SN, not observed in BPD. The BPD group showed a small number of DEGs, including downregulation of TMEM270, METTL27, and CLDN4. These genes are located on chromosome 7 upstream of Elastin (ELN), a gene with complex transcriptional regulation. The non-BPD preterm group revealed no DEGs. <bold>Conclusions:</bold> BPD lung function impairment did not translate into major modifications in BB gene expression compared to healthy term-born. However, some differences were found in a few genes potentially related to the regulation of ELN, an important protein for lung elasticity. We will further investigate this point, combining clinical and other experimental cohort data. Critical genes related to T2 asthma were not dysregulated in BPD, providing crucial insights into potential therapeutic interventions. Prematurity on its own doesn´t impact gene expression in bronchial epithelium.

Karolinska University Hospital (SE), Karolinska Institutet (SE), Stockholm South General Hospital (SE), Sachs' Children and Youth Hospital (SE)
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Neonatal Respiratory Health Research
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