Molecular similarities and differences from human pulmonary fibrosis and corresponding mouse model: MALDI imaging mass spectrometry in comparative medicine
Molecular similarities and differences from human pulmonary fibrosis and corresponding mouse model: MALDI imaging mass spectrometry in comparative medicine
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DOI：
10.1038/labinvest.2017.110
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发表时间：
2018-01-01
影响因子：
5
通讯作者：
Walch, Axel
中科院分区：
文献类型：
--
作者：
Aichler, Michaela;Kunzke, Thomas;Walch, Axel
动物模型可以再现人类疾病的某些特定模型方面，但一些动物模型翻译效果不佳或无法翻译成相应的人类疾病。在这里，我们制定了一种策略来系统地比较人类和小鼠组织，并进行了概念验证实验，以确定特发性肺纤维化患者和博莱霉素诱导的纤维化小鼠模型的分子相似性和差异性。我们的新方法采用人类和小鼠的高通量组织微阵列（TMAs），高分辨率基质辅助激光解吸/电离-傅立叶变换-离子回旋共振-质谱成像（MALDI-FT-ICR-MSI）在特定代谢物水平上对质谱进行空间解析，并采用分层聚类和途径富集分析来识别人类和小鼠病理病变中功能相似/不同的分子模式和途径。我们在人类（n = 83）和小鼠（n = 54）中发现了大量的共同分子（n = 1366）和较少的专有分子。在常见分子中，“抗坏血酸和醛酸盐代谢”途径在人和小鼠病变中具有最高的相似性。这项概念验证研究表明，我们采用可靠且易于执行的实验设计的新策略可以准确地识别可以直接比较动物模型和人类疾病的途径和因素。
Animal models can reproduce some model-specific aspects of human diseases, but some animal models translate poorly or fail to translate to the corresponding human disease. Here, we develop a strategy to systematically compare human and mouse tissues, and conduct a proof-of-concept experiment to identify molecular similarities and differences using patients with idiopathic pulmonary fibrosis and a bleomycin-induced fibrosis mouse model. Our novel approach employs high-throughput tissue microarrays (TMAs) of humans and mice, high-resolution matrix-assisted laser desorption/ionization-Fourier transform-ion cyclotron resonance-mass spectrometry imaging (MALDI-FT-ICR-MSI) to spatially resolve mass spectra at the level of specific metabolites, and hierarchical clustering and pathway enrichment analysis to identify functionally similar/different molecular patterns and pathways in pathological lesions of humans and mice. We identified a large number of common molecules (n = 1366) and fewer exclusive molecules in humans (n = 83) and mice (n = 54). Among the common molecules, the 'ascorbate and aldarate metabolism' pathway had the highest similarity in human and mouse lesions. This proof-of-concept study demonstrates that our novel strategy employing a reliable and easy-to-perform experimental design accurately identifies pathways and factors that can be directly compared between animal models and human diseases.