Integrating 3-omics data analyze rat lung tissue of COPD states and medical intervention by delineation of molecular and pathway alterations
Integrating 3-omics data analyze rat lung tissue of COPD states and medical intervention by delineation of molecular and pathway alterations
复制标题
整合 3 组学数据分析慢性阻塞性肺病 (COPD) 状态的大鼠肺组织，并通过描述分子和通路改变进行医疗干预
DOI：
10.1042/bsr20170042
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发表时间：
2017-06-30
影响因子：
4
通讯作者：
Bai, Yunping
中科院分区：
文献类型：
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作者：
Li, Jiansheng;Zhao, Peng;Bai, Yunping
慢性阻塞性肺疾病(COPD)是一个严重的健康问题。然而，COPD的分子发病机制仍不清楚。在这里，我们探讨了吸烟和细菌感染对COPD大鼠肺组织的分子效应。我们还研究了氨茶碱(APL)对COPD大鼠的治疗作用，以及整合的转录组、蛋白质组和代谢组数据，以全面了解COPD进展的分子机制。通过分子功能和途径分析，COPD和APL大鼠体内调控的基因和蛋白质主要与氧化还原酶、抗氧化活性、能量和脂肪酸代谢有关。此外，我们还鉴定了与能量代谢和氧化应激有关的HUB蛋白，如GAPDH(甘油醛-3-磷酸脱氢酶)、PKM(丙酮酸激酶同工酶M1/M2)和SOD1(超氧化物歧化酶1)。然后，我们确定了慢性阻塞性肺疾病和急性早幼粒细胞白血病大鼠肺组织中显著调控的代谢途径，如花生四烯酸、亚油酸和α-亚麻酸代谢，属于脂质代谢。特别是，我们选择了花生四烯酸代谢来对转录物、蛋白质和代谢物进行更详细的途径分析。我们可以观察到参与花生四烯酸代谢的代谢产物和基因在COPD大鼠增加，在APL治疗的大鼠减少，提示炎症反应在COPD大鼠上调，在APL治疗的大鼠下调。总之，这些全系统的结果表明，COPD的进展及其治疗可能与氧化应激、脂肪和能量代谢紊乱有关。此外，我们还展示了集成组学在阐明与COPD相关的基因、蛋白质和代谢物的变化和紊乱方面的力量。
Chronic obstructive pulmonary disease (COPD) is a serious health problem. However, the molecular pathogenesis of COPD remains unknown. Here, we explored the molecular effects of cigarette smoke and bacterial infection in lung tissues of COPD rats. We also investigated therapeutic effects of aminophylline (APL) on the COPD rats and integrated transcriptome, proteome, and metabolome data for a global view of molecular mechanisms of COPD progression. Using molecular function and pathway analyses, the genes and proteins regulated in COPD and APL-treated rats were mainly attributed to oxidoreductase, antioxidant activity, energy and fatty acid metabolism. Furthermore, we identified hub proteins such as Gapdh (glyceraldehyde-3-phosphate dehydrogenase), Pkm (pyruvate kinase isozymes M1/M2), and Sod1 (superoxide dismutase 1), included in energy metabolism and oxidative stress. Then, we identified the significantly regulated metabolic pathways in lung tissues of COPD- and APL-treated rats, such as arachidonic acid, linoleic acid, and α-linolenic acid metabolism, which belong to the lipid metabolism. In particular, we picked the arachidonic acid metabolism for a more detailed pathway analysis of transcripts, proteins, and metabolites. We could observe an increase in metabolites and genes involved in arachidonic acid metabolism in COPD rats and the decrease in these in APL-treated rats, suggesting that inflammatory responses were up-regulated in COPD rats and down-regulated in APL-treated rats. In conclusion, these system-wide results suggested that COPD progression and its treatment might be associated with oxidative stress, lipid and energy metabolism disturbance. Additionally, we demonstrated the power of integrated omics for the elucidation of genes, proteins, and metabolites’ changes and disorders that were associated with COPD.