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Molecular similarities and differences from human pulmonary fibrosis and corresponding mouse model: MALDI imaging mass spectrometry in comparative medicine.

Lab. Invest. 98, 141-149 (2018)
Open Access Green as soon as Postprint is submitted to ZB.
© 2018 USCAP, Inc All rights reserved. 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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Publication type Article: Journal article
Document type Scientific Article
Keywords Laser Capture Microdissection; Skin Fibroblasts; Ascorbic-acid; Cancer; Tissue; Proteoglycans; Metabolites; Deposition; Pathology; Biology
Reviewing status