Lipidomics reveals dramatic lipid compositional changes in the maturing postnatal lung.
Lipidomics reveals dramatic lipid compositional changes in the maturing postnatal lung.
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DOI：
10.1038/srep40555
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发表时间：
2017-02-01
影响因子：
4.6
通讯作者：
Ansong C
中科院分区：
文献类型：
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作者：
Dautel SE;Kyle JE;Clair G;Sontag RL;Weitz KK;Shukla AK;Nguyen SN;Kim YM;Zink EM;Luders T;Frevert CW;Gharib SA;Laskin J;Carson JP;Metz TO;Corley RA;Ansong C
肺不成熟是早产儿发病率和死亡率的主要原因。了解推动正常肺发育的分子机制可以为如何改善发育中断提供见解。虽然之前已经报道了正常肺发育的转录组和蛋白质组学分析，但缺乏对脂体变化的表征。脂类在肺中扮演着重要的角色，如肺表面活性物质中的二棕榈酰磷脂酰胆碱；然而，特定脂类在正常肺发育和疾病状态中的许多作用尚未很好地确定。在本研究中，我们使用液-质联用技术(LC-MS/MS)研究了小鼠正常出生后肺发育过程中的脂质体。对出生后第7天、第14天和6-8周的小鼠(成年)的肺部进行的脂质组学分析发现，21个脂质亚类中有924种独特的脂类，在不同的发育阶段，脂体发生了戏剧性的变化。我们的数据证实了以前认识到的出生后肺发育的一些方面，并揭示了一些见解，包括鞘磷脂介导的细胞凋亡、炎症和能量储存/使用。互补蛋白质组学、代谢组学和化学成像证实了这些观察结果。这一多组学观点提供了一个独特的资源和对正常肺发育的更深层次的洞察。
Lung immaturity is a major cause of morbidity and mortality in premature infants. Understanding the molecular mechanisms driving normal lung development could provide insights on how to ameliorate disrupted development. While transcriptomic and proteomic analyses of normal lung development have been previously reported, characterization of changes in the lipidome is lacking. Lipids play significant roles in the lung, such as dipalmitoylphosphatidylcholine in pulmonary surfactant; however, many of the roles of specific lipid species in normal lung development, as well as in disease states, are not well defined. In this study, we used liquid chromatography-mass spectrometry (LC-MS/MS) to investigate the murine lipidome during normal postnatal lung development. Lipidomics analysis of lungs from post-natal day 7, day 14 and 6–8 week mice (adult) identified 924 unique lipids across 21 lipid subclasses, with dramatic alterations in the lipidome across developmental stages. Our data confirmed previously recognized aspects of post-natal lung development and revealed several insights, including in sphingolipid-mediated apoptosis, inflammation and energy storage/usage. Complementary proteomics, metabolomics and chemical imaging corroborated these observations. This multi-omic view provides a unique resource and deeper insight into normal pulmonary development.