Identification of vitamin D sensitive pathways during lung development.
Identification of vitamin D sensitive pathways during lung development.
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在肺发育过程中鉴定维生素D敏感途径。
DOI：
10.1186/s12931-016-0362-3
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发表时间：
2016-04-27
影响因子：
5.8
通讯作者：
Zosky GR
中科院分区：
文献类型：
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作者：
Chen L;Wilson R;Bennett E;Zosky GR
我们以前已经表明，维生素D缺乏对肺部发育有不利影响。在这项研究中，我们的目的是确定机制连接维生素D与肺发育使用小鼠模型的饮食操纵。在不同时间点对雌性后代实施安乐死;胚胎日（E）14.5、E17.5或产后日（P）7。收集肺组织用于基于质谱的蛋白质组学分析。无标记定量用于鉴定差异表达的蛋白质，并且ELISA证实所选蛋白质的表达。将来自不同小鼠组的肺固定并处理用于肺结构的体视学评估。在E14.5和E17.5时，维生素D缺乏和维生素D充足小鼠之间的蛋白质表达没有差异，而66种蛋白质在P7肺中差异表达。肺表面活性物质相关蛋白B（SP-B）和过氧化物酶氧还蛋白5（PRDX 5）的表达在维生素D缺乏小鼠的P7肺中减少，而胶原I型α 1（COL 1A 1）的产生在维生素D缺乏小鼠的肺中更高。在三个时间点，维生素D缺乏和维生素D充足小鼠之间的肺体积、实质体积、气隙体积或气隙表面积没有差异。出生后早期蛋白质表达的差异表明，维生素D缺乏可能通过损害肺表面活性物质的产生和抗氧化应激能力以及增加胶原合成来诱导肺泡化阶段的肺结构和功能的改变。这些数据提供了一个合理的机制，母亲维生素D缺乏症与出生后肺功能改变。
We have previously shown that vitamin D deficiency has a detrimental impact on lung development. In this study, we aimed to identify the mechanisms linking vitamin D with lung development using a mouse model of dietary manipulation. Female offspring were euthanized at different time-points; embryonic day (E)14.5, E17.5 or postnatal day (P)7. Lung tissue was collected for mass spectrometry-based proteomic analysis. Label-free quantitation was used to identify the differentially expressed proteins and ELISA confirmed the expression of selected proteins. Lungs from separate groups of mice were fixed and processed for stereological assessment of lung structure. No differences in protein expression between vitamin D deficient and replete mice were detected at E14.5 and E17.5, whereas 66 proteins were differentially expressed in P7 lungs. The expression of pulmonary surfactant-associated protein B (SP-B) and peroxiredoxin 5 (PRDX5) were reduced in P7 lungs of vitamin D deficient mice, while the production of collagen type Ι alpha 1 (COL1A1) was higher in lungs of vitamin D deficient mice. There were no differences in lung volume, parenchymal volume, volume of airspaces or surface area of airspaces between vitamin D deficient and vitamin D replete mice across three time-points. The difference in protein expression during the early postnatal time-point suggests that vitamin D deficiency may induce alterations of lung structure and function in later life during alveolarization stage through impaired pulmonary surfactant production and anti-oxidative stress ability as well as enhanced collagen synthesis. These data provided a plausible mechanism linking maternal vitamin D deficiency with altered postnatal lung function.