Transcriptome Analysis of the Preterm Rabbit Lung after Seven Days of Hyperoxic Exposure

PLoS One. 2015 Aug 28;10(8):e0136569. doi: 10.1371/journal.pone.0136569. eCollection 2015.

Abstract

The neonatal management of preterm born infants often results in damage to the developing lung and subsequent morbidity, referred to as bronchopulmonary dysplasia (BPD). Animal models may help in understanding the molecular processes involved in this condition and define therapeutic targets. Our goal was to identify molecular pathways using the earlier described preterm rabbit model of hyperoxia induced lung-injury. Transcriptome analysis by mRNA-sequencing was performed on lungs from preterm rabbit pups born at day 28 of gestation (term: 31 days) and kept in hyperoxia (95% O2) for 7 days. Controls were preterm pups kept in normoxia. Transcriptomic data were analyzed using Array Studio and Ingenuity Pathway Analysis (IPA), in order to identify the central molecules responsible for the observed transcriptional changes. We detected 2217 significantly dysregulated transcripts following hyperoxia, of which 90% could be identified. Major pathophysiological dysregulations were found in inflammation, lung development, vascular development and reactive oxygen species (ROS) metabolism. To conclude, amongst the many dysregulated transcripts, major changes were found in the inflammatory, oxidative stress and lung developmental pathways. This information may be used for the generation of new treatment hypotheses for hyperoxia-induced lung injury and BPD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Gene Regulatory Networks
  • Hyperoxia / complications
  • Hyperoxia / genetics
  • Hyperoxia / metabolism*
  • Lung / growth & development*
  • Lung / metabolism
  • Lung Injury / etiology
  • Lung Injury / genetics
  • Lung Injury / metabolism*
  • Oxidative Stress
  • Rabbits
  • Transcriptome*

Grants and funding

JDP was a beneficiary of a fundamental clinical research grant of the Fonds Wetenschappelijk Onderzoek Vlaanderen (1801207), and JT from the “Klinische Opleidings- en Onderzoeks-Raad” of the University Hospitals Leuven. Our experimental program is supported by the Flemish Hercules foundation (large infrastructure investments AKUL/09/033), by the KU Leuven (OT/13/115) and by the European Commission via its Erasmus Joint Doctoral program (2013-0040). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.