Potential therapeutic targets in Nrf2-dependent protection against neonatal respiratory distress disease predicted by cDNA microarray analysis and bioinformatics tools.
Potential therapeutic targets in Nrf2-dependent protection against neonatal respiratory distress disease predicted by cDNA microarray analysis and bioinformatics tools.
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DOI：
10.1016/j.cotox.2016.10.006
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发表时间：
2016-12
影响因子：
4.6
通讯作者：
Kleeberger SR
中科院分区：
文献类型：
--
作者：
Cho HY;Wang X;Li J;Bell DA;Kleeberger SR
新生啮齿动物的高氧暴露已成为人类早产儿亚群中发现的支气管肺发育不良（BPD）表型的模型。我们之前使用 Nrf2 缺陷和野生型新生小鼠证明，Nrf2 在肺囊到肺泡成熟过程中调节分子事件，并且在高氧诱导的急性肺损伤、死亡、囊到肺泡转变停滞和肺损伤的发病机制中也具有保护作用。在这篇综述中，我们描述了全基因组转录组分析如何识别 Nrf2 在 BPD 样发病机制中转录调节器官损伤和形态、细胞生长/增殖、脉管系统发育和免疫反应的方式。我们说明了如何使用最近开发的生物信息学工具来识别 BPD 模型中 Nrf2 依赖性调节基因组，并阐明直接的 Nrf2 下游靶标和可能作用于它们的化学物质/药物。这些方法将为 Nrf2 依赖性早产并发症（如 BPD）治疗的有希望的治疗药物提供重要见解。
Hyperoxia exposure of newborn rodents has served as a model for bronchopulmonary dysplasia (BPD) phenotypes found in a sub-population of human premature infants. We previously demonstrated that Nrf2 modulates molecular events during saccular-to-alveolar lung maturation and also has a protective role in the pathogenesis of hyperoxia-induced acute lung injury, mortality, arrest of saccular-to-alveolar transition, and lung injury, using Nrf2-deficient and wild-type neonate mice. In this review, we describe how whole-genome transcriptome analyses can identify the means through which Nrf2 transcriptionally modulates organ injury and morphology, cellular growth/proliferation, vasculature development, and immune response during BPD-like pathogenesis. We illustrate how recently developed bioinformatics tools can be used to identify sets of Nrf2-dependently modulated genes in the BPD model, and elucidate direct Nrf2 downstream targets and chemicals/drugs that may act on them. These approaches will provide significant insights into promising therapeutic agents for Nrf2-dependent treatments of complications of preterm birth like BPD.
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影响因子：
--
作者：
Findlay, Victoria J.;LaRue, Amanda C.;Turner, David P.;Watson, Patricia M.;Watson, Dennis K.
通讯作者：
Watson, Dennis K.
影响因子：
3
作者：
Clark NR;Hu KS;Feldmann AS;Kou Y;Chen EY;Duan Q;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
5.3
作者：
Kobayashi, Makoto;Li, Li;Yamamoto, Masayuki
通讯作者：
Yamamoto, Masayuki
DOI：
10.1164/rccm.200907-1047oc
发表时间：
2010-07-01
影响因子：
24.7
作者：
Cho, Hye-Youn;Gladwell, Wesley;Kleeberger, Steven R.
通讯作者：
Kleeberger, Steven R.
影响因子：
3.6
作者：
Jobe AH
通讯作者：
Jobe AH