{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:03:59Z","timestamp":1790636639293,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:00:00Z","timestamp":1693958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102017\u201004320"],"award-info":[{"award-number":["RGPIN\u20102017\u201004320"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 159455"],"award-info":[{"award-number":["MOP 159455"]}],"id":[{"id":"10.13039\/501100000024","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":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Radiation\u2010induced muscle pathology, characterized by muscle atrophy and fibrotic tissue accumulation, is the most common debilitating late effect of therapeutic radiation exposure particularly in juvenile cancer survivors. In healthy muscle, fibro\/adipogenic progenitors (FAPs) are required for muscle maintenance and regeneration, while in muscle pathology FAPs are precursors for exacerbated extracellular matrix deposition. However, the role of FAPs in radiation\u2010induced muscle pathology has not previously been explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four\u2010week\u2010old Male CBA or C57Bl\/6J mice received a single dose (16\u00a0Gy) of irradiation (IR) to a single hindlimb with the shielded contralateral limb (CLTR) serving as a non\u2010IR control. Mice were sacrificed 3, 7, 14 (acute IR response), and 56\u00a0days post\u2010IR (long\u2010term IR response). Changes in skeletal muscle morphology, myofibre composition, muscle niche cellular dynamics, DNA damage, proliferation, mitochondrial respiration, and metabolism and changes in progenitor cell fate where assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Juvenile radiation exposure resulted in smaller myofibre cross\u2010sectional area, particularly in type I and IIA myofibres (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and reduced the proportion of type I myofibres (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Skeletal muscle fibrosis (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) was evident at 56\u00a0days post\u2010IR. The IR\u2010limb had fewer endothelial cells (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and fibro\u2010adipogenic progenitors (FAPs) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) at 56\u00a0days post\u2010IR. Fewer muscle satellite (stem) cells were detected at 3 and 56\u00a0days in the IR\u2010limb (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). IR induced FAP senescence (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), increased their fibrogenic differentiation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), and promoted their glycolytic metabolism. Further, IR altered the FAP secretome in a manner that impaired muscle satellite (stem) cell differentiation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and fusion (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study suggests that following juvenile radiation exposure, FAPs contribute to long\u2010term skeletal muscle atrophy and fibrosis. These findings provide rationale for investigating FAP\u2010targeted therapies to ameliorate the negative late effects of radiation exposure in skeletal muscle.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13320","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T09:55:02Z","timestamp":1693994102000},"page":"2335-2349","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Radiation induces long\u2010term muscle fibrosis and promotes a fibrotic phenotype in fibro\u2010adipogenic progenitors"],"prefix":"10.1002","volume":"14","author":[{"given":"Nicolas","family":"Collao","sequence":"first","affiliation":[{"name":"School of Human Kinetics, Faculty of Health Science University of Ottawa  Ottawa Canada"},{"name":"\u00c9ric Poulin Centre for Neuromuscular Disease University of Ottawa  Ottawa 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