TY - JOUR
T1 - Proteomics of muscle microdialysates identifies potential circulating biomarkers in facioscapulohumeral muscular dystrophy
AU - Carregari, Victor Corasolla
AU - Monforte, Mauro
AU - Di Maio, Giuseppe
AU - Pieroni, Luisa
AU - Urbani, Andrea
AU - Ricci, Enzo
AU - Tasca, Giorgio
N1 - Funding Information:
Funding: This study was funded by the FSHD Society Grant FSHS-82017-6 to G.T.
Publisher Copyright:
© 2020 by the authors. Li-censee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Facioscapulohumeral muscular dystrophy (FSHD) is caused by a complex epigenetic mechanism finally leading to the misexpression of DUX4 in skeletal muscle. Detecting DUX4 and quantifying disease progression in FSHD is extremely challenging, thus increasing the need for surrogate biomarkers. We applied a shotgun proteomic approach with two different setups to ana-lyze the protein repertoire of interstitial fluids obtained from 20 muscles in different disease stages classified by magnetic resonance imaging (MRI) and serum samples from 10 FSHD patients. A total of 1156 proteins were identified in the microdialysates by data independent acquisition, 130 of which only found in muscles in active disease stage. Proteomic profiles were able to distinguish FSHD patients from controls. Two innate immunity mediators (S100-A8 and A9) and Dermcidin were upregulated in muscles with active disease and selectively present in the sera of FSHD patients. Structural muscle and plasminogen pathway proteins were downregulated. Together with the upstream inhibition of myogenic factors, this suggests defective muscle regeneration and increased fibrosis in early/active FSHD. Our MRI targeted exploratory approach confirmed that inflammatory response has a prominent role, together with impaired muscle regeneration, before clear muscle wasting occurs. We also identified three proteins as tissue and possibly circulating biomarkers in FSHD.
AB - Facioscapulohumeral muscular dystrophy (FSHD) is caused by a complex epigenetic mechanism finally leading to the misexpression of DUX4 in skeletal muscle. Detecting DUX4 and quantifying disease progression in FSHD is extremely challenging, thus increasing the need for surrogate biomarkers. We applied a shotgun proteomic approach with two different setups to ana-lyze the protein repertoire of interstitial fluids obtained from 20 muscles in different disease stages classified by magnetic resonance imaging (MRI) and serum samples from 10 FSHD patients. A total of 1156 proteins were identified in the microdialysates by data independent acquisition, 130 of which only found in muscles in active disease stage. Proteomic profiles were able to distinguish FSHD patients from controls. Two innate immunity mediators (S100-A8 and A9) and Dermcidin were upregulated in muscles with active disease and selectively present in the sera of FSHD patients. Structural muscle and plasminogen pathway proteins were downregulated. Together with the upstream inhibition of myogenic factors, this suggests defective muscle regeneration and increased fibrosis in early/active FSHD. Our MRI targeted exploratory approach confirmed that inflammatory response has a prominent role, together with impaired muscle regeneration, before clear muscle wasting occurs. We also identified three proteins as tissue and possibly circulating biomarkers in FSHD.
KW - Biomarkers
KW - Facioscapulohumeral muscular dystrophy
KW - FSHD
KW - Inflammatory response
KW - Proteomics
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U2 - 10.3390/ijms22010290
DO - 10.3390/ijms22010290
M3 - Article
AN - SCOPUS:85098846786
VL - 22
SP - 1
EP - 17
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 1
M1 - 290
ER -