MOLECULAR SIMILARITIES AND DIFFERENCES FROM HUMAN PULMONARY FIBROSIS AND CORRESPONDING MOUSE MODEL: MALDI IMAGING MASS SPECTROMETRY IN COMPARATIVE MEDICINE
Michaela Aichler, Thomas Kunzke, Achim Buck, Na Sun, Maximilian Ackermann, Danny Jonigk, Andreas Gaumann and Axel Walch. (19-02-2018).Laboratory Investigation, 2018, doi:10.1038/labinvest.2017.110
Research Area C
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 highthroughput 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-toperform experimental design accurately identifies pathways and factors that can be directly compared between animal models and human diseases.