辐射引起的肌肉病理学特点是肌肉萎缩和纤维组织积累，在幼年癌症幸存者中特别普遍。在健康的肌肉中，纤维/脂肪成熟前体（FAPs）对于肌肉的维持和再生是必需的，而在肌肉病理学中，FAPs是导致过度细胞外基质堆积的前体。然而，FAPs在辐射引起的肌肉病理学中的作用尚未被研究。 四周大的雄性CBA或C57Bl/6J小鼠在一个保护装置遮盖的对侧肢体（CLTR）作为非辐射（IR）对照，接受一次性辐照（16 Gy）到单个后腿。小鼠在IR后3、7、14天（急性IR反应）和56天（长期IR反应）被牺牲。评估骨骼肌形态学、肌肉纤维组成、肌肉适配环境细胞动力学、DNA损伤、增殖、线粒体呼吸和代谢的变化以及祖细胞命运的变化。 幼年辐射暴露导致肌肉横截面积变小，特别是I型和IIA型肌纤维（P < 0.05），并降低I型肌纤维的比例（P < 0.05）。在IR后56天，出现肌肉纤维化（P < 0.05）。IR腿部在IR后56天内的内皮细胞（P < 0.05）和纤维/脂肪成熟前体（FAPs）（P < 0.05）较少。在IR腿部，肌肉卫星（干细胞）细胞在3天和56天时检测到更少（P < 0.05）。IR诱导FAP衰老（P < 0.05），增加它们的纤维成熟分化（P < 0.01）并促进它们的糖酵解代谢。此外，IR以一种方式改变了FAP分泌物，导致肌肉卫星（干细胞）细胞分化（P < 0.05）和融合（P < 0.05）受损。 我们的研究表明，在幼年辐射暴露后，FAPs会导致骨骼肌长期萎缩和纤维化。这些发现为探究以FAP为靶点的治疗策略，以改善辐射暴露对骨骼肌的负面延迟效应提供了合理基础。 © 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.

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.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.Juvenile radiation exposure resulted in smaller myofibre cross-sectional area, particularly in type I and IIA myofibres (P < 0.05) and reduced the proportion of type I myofibres (P < 0.05). Skeletal muscle fibrosis (P < 0.05) was evident at 56 days post-IR. The IR-limb had fewer endothelial cells (P < 0.05) and fibro-adipogenic progenitors (FAPs) (P < 0.05) at 56 days post-IR. Fewer muscle satellite (stem) cells were detected at 3 and 56 days in the IR-limb (P < 0.05). IR induced FAP senescence (P < 0.05), increased their fibrogenic differentiation (P < 0.01), and promoted their glycolytic metabolism. Further, IR altered the FAP secretome in a manner that impaired muscle satellite (stem) cell differentiation (P < 0.05) and fusion (P < 0.05).Our study suggests that following juvenile radiation exposure, FAPs contribute to long-term skeletal muscle atrophy and fibrosis. These findings provide rationale for investigating FAP-targeted therapies to ameliorate the negative late effects of radiation exposure in skeletal muscle.© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.