Genome-Wide Analysis of DNA Methylation in Hyperoxia-Exposed Newborn Rat Lung

Chung Ming Chen, Yi Chun Liu, Yue Jun Chen, Hsiu Chu Chou

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purpose: Oxygen therapy is often required to treat newborn infants with respiratory disorders. Prolonged exposure of neonatal rats to hyperoxia reduced alveolar septation, increased terminal air space size, and increased lung fibrosis; these conditions are very similar to those of human bronchopulmonary dysplasia. Epigenetic regulation of gene expression plays a crucial role in bronchopulmonary dysplasia development. Method: We reared Sprague–Dawley rat pups in either room air (RA, n = 24) or an atmosphere containing 85% O2 (n = 26) from Postnatal Days 1 to 14. Methylated DNA immunoprecipitation (MeDIP) was used to analyze genome-wide DNA methylation in lung tissues of neonatal rats. Hyperoxia-exposed rats exhibited larger air spaces and thinner septa than RA-exposed rats did on Postnatal Day 14. The rats exposed to hyperoxia exhibited significantly higher mean linear intercepts than did the rats exposed to RA. We applied MeDIP next-generation sequencing for profiling changes in DNA methylation in the rat lungs exposed to hyperoxia and RA. We performed bioinformatics and pathway analyses on the raw sequencing data to identify differentially methylated candidate genes. Results: Our in vivo model revealed that neonatal hyperoxia exposure arrested alveolarization on Postnatal Day 14. We found that the ErbB, actin cytoskeleton, and focal adhesion signaling pathways are epigenetically modulated by exposure to hyperoxia. We demonstrated that hyperoxia exposure contribute in delaying lung development through an epigenetic mechanism by disrupting the expression of genes in lungs that might be involved in alveolarization. Conclusions: These data indicate that aberrant DNA methylation and deregulation of the actin cytoskeleton and focal adhesion pathways of lung tissues may be involved in the pathophysiology of hyperoxia-induced arrested alveolarization.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalLung
DOIs
Publication statusAccepted/In press - Jul 8 2017

Keywords

  • Alveolarization
  • DNA methylation
  • Hyperoxia
  • Mean linear intercept
  • MeDIP
  • Radial alveolar count

ASJC Scopus subject areas

  • Medicine(all)

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