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

Cecilie Revhaug1, Miroslaw Bik-Multanowski2, Magdalena Zasada3

  • 1Department of Pediatric Research, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway, cecrev@rr-research.no.

Neonatology
|August 28, 2019
PubMed

Insights

Bronchopulmonary dysplasia (BPD) in preterm infants involves complex gene regulation. This study found that hyperoxia alters immune gene expression and DNA methylation in mice, potentially explaining increased infection susceptibility in BPD.

Area of Science:

  • Neonatal Medicine
  • Pulmonology
  • Immunology

Background:

  • Bronchopulmonary dysplasia (BPD) is a prevalent complication of preterm birth, characterized by impaired lung development.
  • BPD is associated with significant long-term respiratory morbidity, including frequent infections and reduced lung function.
  • The pathogenesis of BPD involves intricate genetic and epigenetic regulatory mechanisms.

Purpose of the Study:

  • To investigate the relationship between gene expression and DNA methylation in the immune system of a mouse model of BPD.
  • To understand the epigenetic changes following hyperoxia exposure and subsequent recovery in the context of BPD.

Main Methods:

  • A mouse model was used, exposing newborn pups to hyperoxia (85% O2) for 14 days, followed by 14 days in room air.
  • Lung tissue was analyzed for gene expression (transcriptome) and DNA methylation (methylome) using microarray technology.
  • Focus was placed on immune system-related genes and signaling pathways.

Main Results:

  • Hyperoxia exposure significantly altered the expression of immune system-related genes in mouse lungs.
  • Key pathways affected include B cell receptor signaling, cytokine-cytokine receptor interaction, and PI3K-AKT signaling.
  • Significant DNA hypermethylation was observed in genes within the PI3K-AKT pathway and other immune-related genes.

Conclusions:

  • Dysregulated gene expression in the immune system, driven by oxygen-induced damage, may contribute to the heightened susceptibility to respiratory infections in premature infants with BPD.
  • Epigenetic modifications, specifically DNA hypermethylation, play a role in the altered immune response observed in BPD.
  • These findings highlight potential therapeutic targets for mitigating respiratory complications in BPD.
Abstract

Keywords:
EpigeneticsExperimental bronchopulmonary dysplasiaGene regulationImmune system regulation

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