Immune System Regulation Affected by a Murine Experimental Model of Bronchopulmonary Dysplasia: Genomic and Epigenetic Findings.

Autor:	Revhaug C; Department of Pediatric Research, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway, cecrev@rr-research.no., Bik-Multanowski M; Department of Medical Genetics, Institute of Pediatrics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland., Zasada M; Department of Pediatrics, Institute of Pediatrics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland., Rognlien AGW; Department of Pediatric Research, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway., Günther CC; Norwegian Computing Center, Oslo, Norway., Ksiązek T; Department of Medical Genetics, Institute of Pediatrics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland., Madetko-Talowska A; Department of Medical Genetics, Institute of Pediatrics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland., Szewczyk K; Department of Medical Genetics, Institute of Pediatrics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland., Grabowska A; Department of Medical Genetics, Institute of Pediatrics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland., Kwinta P; Department of Pediatrics, Institute of Pediatrics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland., Pietrzyk JJ; Department of Medical Genetics, Institute of Pediatrics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland.; Department of Pediatrics, Institute of Pediatrics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland., Baumbusch LO; Department of Pediatric Research, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway., Saugstad OD; Department of Pediatric Research, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	Neonatology [Neonatology] 2019; Vol. 116 (3), pp. 269-277. Date of Electronic Publication: 2019 Aug 27.
DOI:	10.1159/000501461
Abstrakt:	Background: Bronchopulmonary dysplasia (BPD) is a common cause of abrupted lung development after preterm birth. BPD may lead to increased rehospitalization, more severe and frequent respiratory infections, and life-long reduced lung function. The gene regulation in lungs with BPD is complex, with various genetic and epigenetic factors involved. Objectives: The aim of this study was to examine the regulatory relation between gene expression and the epigenome (DNA methylation) relevant for the immune system after hyperoxia followed by a recovery period in air using a mouse model of BPD. Methods: Newborn mice pups were subjected to an immediate hyperoxic condition from birth and kept at 85% O2 levels for 14 days followed by a 14-day period in room air. Next, mice lung tissue was used for RNA and DNA extraction with subsequent microarray-based assessment of lung transcriptome and supplementary methylome analysis. Results: The immune system-related transcriptomeregulation was affected in mouse lungs after hyperoxia. A high proportion of genes relevant in the immune system exhibited significant expression alterations, e.g., B cell-specific genes central to the cytokine-cytokine receptor interaction, the PI3K-AKT, and the B cell receptor signaling pathways. The findings were accompanied by significant DNA hypermethylation observed in the PI3K-AKT pathway and immune system-relevant genes. Conclusions: Oxygen damage could be partly responsible for the increased susceptibility and abnormal response to respiratory viruses and infections seen in premature babies with BPD through dysregulated genes. (© 2019 S. Karger AG, Basel.)
Databáze:	MEDLINE
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