1. Radiation induces long‐term muscle fibrosis and promotes a fibrotic phenotype in fibro‐adipogenic progenitors
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Nicolas Collao, Donna D'Souza, Laura Messeiller, Evan Pilon, Jessica Lloyd, Jillian Larkin, Matthew Ngu, Alexanne Cuillerier, Alexander E. Green, Keir J. Menzies, Yan Burelle, and Michael De Lisio
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Atrophy ,Differentiation ,Extracellular matrix ,Mesenchymal progenitors ,Metabolism ,Myofibroblast ,Diseases of the musculoskeletal system ,RC925-935 ,Human anatomy ,QM1-695 - Abstract
Abstract Background Radiation‐induced 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‐induced muscle pathology has not previously been explored. Methods Four‐week‐old Male CBA or C57Bl/6J mice received a single dose (16 Gy) of irradiation (IR) to a single hindlimb with the shielded contralateral limb (CLTR) serving as a non‐IR control. Mice were sacrificed 3, 7, 14 (acute IR response), and 56 days post‐IR (long‐term 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. Results Juvenile radiation exposure resulted in smaller myofibre cross‐sectional area, particularly in type I and IIA myofibres (P
- Published
- 2023
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