{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T09:37:49Z","timestamp":1787391469063,"version":"build-2736575974"},"reference-count":130,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T00:00:00Z","timestamp":1735948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANID Fondecyt Regular","award":["#1240485"],"award-info":[{"award-number":["#1240485"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>DUX4 is typically a repressed transcription factor, but its aberrant activation in Facioscapulohumeral Muscular Dystrophy (FSHD) leads to cell death by disrupting muscle homeostasis. This disruption affects crucial processes such as myogenesis, sarcolemma integrity, gene regulation, oxidative stress, immune response, and many other biological pathways. Notably, these disrupted processes have been associated, in other pathological contexts, with the presence of connexin (Cx) hemichannels\u2014transmembrane structures that mediate communication between the intracellular and extracellular environments. Thus, hemichannels have been implicated in skeletal muscle atrophy, as observed in human biopsies and animal models of Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, and Dysferlinopathies, suggesting a potentially shared mechanism of muscle atrophy that has not yet been explored in FSHD. Despite various therapeutic strategies proposed to manage FSHD, no treatment or cure is currently available. This review summarizes the current understanding of the mechanisms underlying FSHD progression, with a focus on hormones, inflammation, reactive oxygen species (ROS), and mitochondrial function. Additionally, it explores the potential of targeting hemichannels as a therapeutic strategy to slow disease progression by preventing the spread of pathogenic factors between muscle cells.<\/jats:p>","DOI":"10.3390\/ijms26010373","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T08:08:52Z","timestamp":1736150932000},"page":"373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Unexplored Role of Connexin Hemichannels in Promoting Facioscapulohumeral Muscular Dystrophy Progression"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4581-5638","authenticated-orcid":false,"given":"Macarena","family":"D\u00edaz-Ubilla","sequence":"first","affiliation":[{"name":"Instituto de Ciencias e Innovaci\u00f3n en Medicina, Facultad de Medicina, Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 7550000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2562-6686","authenticated-orcid":false,"given":"Mauricio A.","family":"Retamal","sequence":"additional","affiliation":[{"name":"Programa de Comunicaci\u00f3n Celular en C\u00e1ncer, Facultad de Medicina, Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 7550000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1212\/WNL.44.3_Part_1.442","article-title":"Facioscapulohumeral muscular dystrophy (FSHD): Design of natural history study and results of baseline testing","volume":"44","author":"Tawil","year":"1994","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s10048-019-00575-4","article-title":"Facioscapulohumeral muscular dystrophy (FSHD) molecular diagnosis: From traditional technology to the NGS era","volume":"20","author":"Zampatti","year":"2019","journal-title":"Neurogenetics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.bbadis.2014.05.021","article-title":"Facioscapulohumeral muscular dystrophy","volume":"1852","author":"Sacconi","year":"2015","journal-title":"Biochim. 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