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Proteomics of Muscle Microdialysates Identifies Potential Circulating Biomarkers in Facioscapulohumeral Muscular Dystrophy

Lookup NU author(s): Professor Giorgio TascaORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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 analyze 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.

Publication metadata

Author(s): Corasolla Carregari V, Monforte M, Di Maio G, Pieroni L, Urbani A, Ricci E, Tasca G

Publication type: Article

Publication status: Published

Journal: International Journal of Molecular Sciences

Year: 2021

Volume: 22

Issue: 1

Print publication date: 01/01/2021

Online publication date: 30/12/2020

Acceptance date: 25/12/2020

Date deposited: 27/02/2023

ISSN (electronic): 1422-0067

Publisher: MDPI AG


DOI: 10.3390/ijms22010290

PubMed id: 33396627


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