Metabolic heterogeneity of idiopathic pulmonary fibrosis: a metabolomic study.
Metabolic heterogeneity of idiopathic pulmonary fibrosis: a metabolomic study.
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DOI：
10.1136/bmjresp-2017-000183
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发表时间：
2017
影响因子：
4.1
通讯作者：
de Perrot M
中科院分区：
文献类型：
--
作者：
Zhao YD;Yin L;Archer S;Lu C;Zhao G;Yao Y;Wu L;Hsin M;Waddell TK;Keshavjee S;Granton J;de Perrot M
特发性肺纤维化（IPF）是一种病因不明的慢性致死性疾病，其特征是肺组织的进行性纤维化形成。我们假设IPF中被破坏的代谢途径有助于疾病的发病机制。采用质谱法对人IPF进行代谢组学分析（IPF肺=8；供体肺=8）。利用微阵列技术检测关键代谢酶的基因表达。与正常对照相比，IPF样品中发现的108种代谢物水平发生改变，其中48种显著增加，而60种显著降低。特异性代谢途径介导IPF重构，鞘脂代谢途径下调，精氨酸代谢途径上调。此外，与对照组相比，IPF样本的糖酵解、线粒体β -氧化和三羧酸循环被破坏，胆汁酸、血红素和谷氨酸/天冬氨酸代谢被改变。我们的研究结果表明，肺结构重塑过程中能量消耗的代谢途径发生了改变，这可能有助于IPF的发病机制。我们认为，这是首次同时系统地测量人类严重IPF肺中涉及9种代谢途径的代谢物变化的报道。代谢物的测定可能有助于IPF的诊断和预后。
Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disease of unknown cause characterised by progressive fibrotic formation in lung tissue. We hypothesise that disrupted metabolic pathways in IPF contribute to disease pathogenesis. Metabolomics of human IPF was performed using mass spectroscopy (IPF lung=8; donor lung=8). Gene expression of key metabolic enzymes was measured using microarrays. Of the 108 metabolites whose levels were found altered, 48 were significantly increased, whereas 60 were significantly decreased in IPF samples compared with normal controls. Specific metabolic pathways mediating the IPF remodelling were found with a downregulated sphingolipid metabolic pathway but an upregulated arginine pathway in IPF. In addition, disrupted glycolysis, mitochondrial beta-oxidation and tricarboxylic acid cycle, altered bile acid, haem and glutamate/aspartate metabolism were found in IPF samples compared with control. Our results show alterations in metabolic pathways for energy consumption during lung structural remodelling, which may contribute to IPF pathogenesis. We believe that this is the first report of simultaneously and systemically measuring changes of metabolites involving nine metabolic pathways in human severe IPF lungs. The measurement of the metabolites may serve in the future diagnosis and prognosis of IPF.