Journal
LABORATORY INVESTIGATION
Volume 98, Issue 1, Pages 141-149Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/labinvest.2017.110
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Funding
- Ministry of Education and Research of the Federal Republic of Germany (BMBF) [01ZX1310B, 01KT16015]
- Deutsche Forschungsgemeinschaft [SFB 824 TP Z02 / C4, CRC/TRR 205 S01]
- Deutsche Krebshilfe [70112617]
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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.
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