Laboratory of Bioinformatics, Artificial Intelligence Center for Health and Biomedical Research (ArCHER), National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Japan.
FEBS Open Bio. 2020 Nov;10(11):2427-2436. doi: 10.1002/2211-5463.12982. Epub 2020 Oct 5.
Idiopathic pulmonary fibrosis (IPF) is a severe lung disease with poor survival that warrants early and precise diagnosis for timely therapeutic intervention. Despite accumulating genomic, transcriptomic, proteomic, and lipidomic data on IPF, evidence from water-soluble metabolomics is limited. To identify biomarkers for IPF from water-soluble metabolomic data, we measured the levels of various metabolites in bronchoalveolar lavage fluid (BALF) and serum samples from a bleomycin-induced murine pulmonary fibrotic model using gas chromatography/mass spectrometry. Thirty-two of 73 BALF metabolites and 29 of 74 serum metabolites were annotated. We observed that the levels of proline and methionine were higher in BALF but lower in serum than those in the control. Furthermore, analysis of public RNA-Seq data from the lungs of patients with IPF revealed that proline- and methionine-related genes were significantly upregulated compared to those in the lungs of healthy controls. These results suggest that proline and methionine may be potential biomarkers for IPF and may help to deepen our understanding of the pathophysiology of the disease. Based on our results, we propose a model capable of recapitulating the proline and methionine metabolism of fibrotic lungs, thereby providing better means for studying the disease and developing novel therapeutic strategies for IPF.
特发性肺纤维化（IPF）是一种严重的肺部疾病，生存预后差，需要早期、准确的诊断以便及时进行治疗干预。尽管在 IPF 的基因组、转录组、蛋白质组和脂质组学方面积累了大量数据，但水溶性代谢组学方面的证据有限。为了从水溶性代谢组学数据中鉴定出 IPF 的生物标志物，我们使用气相色谱/质谱法测量了博莱霉素诱导的小鼠肺纤维化模型的支气管肺泡灌洗液（BALF）和血清样本中的各种代谢物水平。在 73 种 BALF 代谢物中，有 32 种被注释；在 74 种血清代谢物中，有 29 种被注释。我们观察到，BALF 中的脯氨酸和蛋氨酸水平高于对照组，而血清中的水平则低于对照组。此外，对来自 IPF 患者肺部的公共 RNA-Seq 数据的分析表明，与健康对照组相比，脯氨酸和蛋氨酸相关基因显著上调。这些结果表明，脯氨酸和蛋氨酸可能是 IPF 的潜在生物标志物，并可能有助于加深我们对疾病病理生理学的理解。基于我们的结果，我们提出了一个能够再现纤维化肺部脯氨酸和蛋氨酸代谢的模型，从而为研究该疾病和开发针对 IPF 的新治疗策略提供了更好的方法。
