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The disease, caused by the lack of functional dystrophin, is characterized by irreversible impairment of muscle functions, with the diaphragm affected earlier and more severely than other skeletal muscles. We applied a label-free (LF) method and the more thorough tandem mass tag (TMT)-based method to analyze differentially expressed proteins in the diaphragm of 6-week-old mdx mice. The comparison of both methods revealed 88 commonly changed proteins. A more in-depth analysis of the TMT-based method showed 953 significantly changed proteins, with 867 increased and 86 decreased in dystrophic animals (q-value &lt; 0.05, fold-change threshold: 1.5). Consequently, several dysregulated processes were demonstrated, including the immune response, fibrosis, translation, and programmed cell death. Interestingly, in the dystrophic diaphragm, we found a significant decrease in the expression of enzymes generating hydrogen sulfide (H2S), suggesting that alterations in the metabolism of this gaseous mediator could modulate DMD progression, which could be a potential target for pharmacological intervention.<\/jats:p>","DOI":"10.3390\/biom13111648","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T02:20:37Z","timestamp":1699928437000},"page":"1648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Proteome Profiling of the Dystrophic mdx Mice Diaphragm"],"prefix":"10.3390","volume":"13","author":[{"given":"Olga","family":"Mucha","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7 Street, 30-387 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0142gorzata","family":"Myszka","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7 Street, 30-387 Krak\u00f3w, Poland"},{"name":"Doctoral School of Exact and Natural Sciences, \u0141ojasiewicza 11 Street, 30-348 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulina","family":"Podkalicka","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7 Street, 30-387 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianka","family":"\u015awiderska","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawi\u0144skiego 5a Street, 02-106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6599-901X","authenticated-orcid":false,"given":"Agata","family":"Malinowska","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawi\u0144skiego 5a Street, 02-106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5687-0839","authenticated-orcid":false,"given":"J\u00f3zef","family":"Dulak","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7 Street, 30-387 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3523-3560","authenticated-orcid":false,"given":"Agnieszka","family":"\u0141oboda","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7 Street, 30-387 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1055\/s-0032-1329199","article-title":"The Muscular Dystrophies","volume":"32","author":"Flanigan","year":"2012","journal-title":"Semin. 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