Salaets Thomas, Richter Jute, Brady Paul, Jimenez Julio, Nagatomo Taro, Deprest Jan, Toelen Jaan
University Hospitals Leuven, Department of Pediatrics, Leuven, Belgium.
Department of Development and Regeneration, Research Unit Fetus Placenta Neonate, Group of Biomedical Sciences, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Obstetrics and Gynecology, Leuven, Belgium.
PLoS One. 2015 Aug 28;10(8):e0136569. doi: 10.1371/journal.pone.0136569. eCollection 2015.
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.
早产婴儿的新生儿管理常常导致发育中的肺部受损及随后的发病情况，即支气管肺发育不良（BPD）。动物模型可能有助于理解该病症所涉及的分子过程并确定治疗靶点。我们的目标是利用先前描述的早产兔高氧诱导肺损伤模型来识别分子途径。对妊娠28天（足月：31天）出生并在高氧（95% O₂）环境中饲养7天的早产兔幼崽的肺部进行了mRNA测序转录组分析。对照组为处于常氧环境中的早产幼崽。使用Array Studio和 Ingenuity Pathway Analysis（IPA）对转录组数据进行分析，以识别导致观察到的转录变化的核心分子。高氧处理后，我们检测到2217个显著失调的转录本，其中90%能够被识别。在炎症、肺发育、血管发育和活性氧（ROS）代谢方面发现了主要的病理生理失调。总之，在众多失调的转录本中，在炎症、氧化应激和肺发育途径中发现了主要变化。这些信息可用于生成针对高氧诱导肺损伤和BPD的新治疗假说。
