{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:23:12Z","timestamp":1789690992021,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI21\/00935"],"award-info":[{"award-number":["PI21\/00935"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/00451"],"award-info":[{"award-number":["PI18\/00451"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/00498"],"award-info":[{"award-number":["PI18\/00498"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,4]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Inclusion body myositis (IBM) is an inflammatory myopathy clinically characterized by proximal and distal muscle weakness, with inflammatory infiltrates, rimmed vacuoles and mitochondrial changes in muscle histopathology. There is scarce knowledge on IBM aetiology, and non\u2010established biomarkers or effective treatments are available, partly due to the lack of validated disease models.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We have performed transcriptomics and functional validation of IBM muscle pathological hallmarks in fibroblasts from IBM patients (\n n<\/jats:italic>\n \u00a0=\u00a014) and healthy controls (\n n<\/jats:italic>\n \u00a0=\u00a012), paired by age and sex. The results comprise an mRNA\u2010seq, together with functional inflammatory, autophagy, mitochondrial and metabolic changes between patients and controls.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Gene expression profile of IBM vs control fibroblasts revealed 778 differentially expressed genes (\n P<\/jats:italic>\n \u2010value adj\u00a0<\u00a00.05) related to inflammation, mitochondria, cell cycle regulation and metabolism. Functionally, an increased inflammatory profile was observed in IBM fibroblasts with higher supernatant cytokine secretion (three\u2010fold increase). Autophagy was reduced considering basal protein mediators (18.4% reduced), time\u2010course autophagosome formation (LC3BII 39% reduced,\n P<\/jats:italic>\n \u2010value\u00a0<\u00a00.05), and autophagosome microscopic evaluation. Mitochondria displayed reduced genetic content (by 33.9%,\n P<\/jats:italic>\n \u2010value\u00a0<\u00a00.05) and function (30.2%\u2010decrease in respiration, 45.6%\u2010decline in enzymatic activity (\n P<\/jats:italic>\n \u2010value\u00a0<\u00a00.001), 14.3%\u2010higher oxidative stress, 135.2%\u2010increased antioxidant defence (\n P<\/jats:italic>\n \u2010value\u00a0<\u00a00.05), 11.6%\u2010reduced mitochondrial membrane potential (\n P<\/jats:italic>\n \u2010value\u00a0<\u00a00.05) and 42.8%\u2010reduced mitochondrial elongation (\n P<\/jats:italic>\n \u2010value\u00a0<\u00a00.05)). In accordance, at the metabolite level, organic acid showed a 1.8\u2010fold change increase, with conserved amino acid profile. Correlating to disease evolution, oxidative stress and inflammation emerge as potential markers of prognosis.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n These findings confirm the presence of molecular disturbances in peripheral tissues from IBM patients and prompt patients' derived fibroblasts as a promising disease model, which may eventually be exported to other neuromuscular disorders. We additionally identify new molecular players in IBM associated with disease progression, setting the path to deepen in disease aetiology, in the identification of novel biomarkers or in the standardization of biomimetic platforms to assay new therapeutic strategies for preclinical studies.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.13178","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T01:45:56Z","timestamp":1677721556000},"page":"964-977","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Unravelling inclusion body myositis using a patient\u2010derived fibroblast model"],"prefix":"10.1002","volume":"14","author":[{"given":"Judith","family":"Cant\u00f3\u2010Santos","sequence":"first","affiliation":[{"name":"Muscle Research and Mitochondrial Function Lab, Centre de Recerca Biom\u00e8dica CELLEX \u2010 Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona Barcelona Spain"},{"name":"Department of Internal Medicine Hospital Clinic of Barcelona Barcelona Spain"},{"name":"CIBERER\u2014Spanish Biomedical Research Centre in Rare Diseases Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Valls\u2010Roca","sequence":"additional","affiliation":[{"name":"Muscle Research and Mitochondrial Function Lab, Centre de Recerca Biom\u00e8dica CELLEX \u2010 Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona Barcelona Spain"},{"name":"Department of Internal Medicine Hospital Clinic of Barcelona Barcelona Spain"},{"name":"CIBERER\u2014Spanish Biomedical Research Centre in Rare Diseases Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Tob\u00edas","sequence":"additional","affiliation":[{"name":"Muscle Research and 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