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)
© 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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Laser Capture Microdissection; Skin Fibroblasts; Ascorbic-acid; Cancer; Tissue; Proteoglycans; Metabolites; Deposition; Pathology; Biology
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2018
Prepublished im Jahr
2017
HGF-Berichtsjahr
2017
ISSN (print) / ISBN
0023-6837
e-ISSN
1530-0307
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 98,
Heft: 1,
Seiten: 141-149
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Nature Publishing Group
Verlagsort
New York
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0000-00-00
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Prüfer
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0000-00-00
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0000-00-00
Anmelder/Inhaber
weitere Inhaber
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Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30205 - Bioengineering and Digital Health
Forschungsfeld(er)
Enabling and Novel Technologies
PSP-Element(e)
G-500390-001
Förderungen
Copyright
Erfassungsdatum
2017-10-18