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Identification of marker proteins of muscular dystrophy in the urine proteome from the mdx-4cv model of dystrophinopathy

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Abstract

Since the protein constituents of urine present a dynamic proteome that can reflect a variety of disease-related alterations in the body, the mass spectrometric survey of proteome-wide changes in urine promises new insights into pathogenic mechanisms. Urine can be investigated in a completely non-invasive way and provides valuable biomedical information on body-wide changes. In this report, we have focused on the urine proteome in X-linked muscular dystrophy using the established mdx-4cv mouse model of dystrophinopathy. In order to avoid potential artefacts due to the manipulation of the biofluid proteome prior to mass spectrometry, crude urine specimens were analyzed without the prior usage of centrifugation steps or concentration procedures. Comparative proteomics revealed 21 increased and 8 decreased proteins out of 870 identified urinary proteoforms using 50 μl of biofluid per investigated sample, i.e. 14 wild type versus 14 mdx-4cv specimens. Promising marker proteins that were almost exclusively found in mdx-4cv urine included nidogen, parvalbumin and titin. Interestingly, the mass spectrometric identification of urine-associated titin revealed a wide spread of peptides over the sequence of this giant muscle protein. The newly established urinomic signature of dystrophinopathy might be helpful for the design of non-invasive assays to improve diagnosis, prognosis, therapy-monitoring and evaluation of potential harmful side effects of novel treatments in the field of muscular dystrophy research.

Graphical abstract: Identification of marker proteins of muscular dystrophy in the urine proteome from the mdx-4cv model of dystrophinopathy

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Supplementary files

Article information


Submitted
11 Dec 2019
Accepted
15 Mar 2020
First published
18 Mar 2020

Mol. Omics, 2020, Advance Article
Article type
Research Article

Identification of marker proteins of muscular dystrophy in the urine proteome from the mdx-4cv model of dystrophinopathy

S. Gargan, P. Dowling, M. Zweyer, D. Swandulla and K. Ohlendieck, Mol. Omics, 2020, Advance Article , DOI: 10.1039/C9MO00182D

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