Skeletal muscles can undergo atrophy and/or programmed cell death (PCD) during development or in response to a wide range of insults, including immobility, cachexia, and spinal cord injury. However, the protracted nature of atrophy and the presence of multiple cell types within the tissue complicates molecular analyses. One model that does not suffer from these limitations is the intersegmental muscle (ISM) of the tobacco hawkmoth Manduca sexta. Three days before the adult eclosion (emergence) at the end of metamorphosis, the ISMs initiate a non-pathological program of atrophy that results in a 40% loss of mass. The ISMs then generate the eclosion behaviour and initiate a non-apoptotic PCD during the next 30 hours. We have performed a comprehensive transcriptomics analysis of all mRNAs and microRNAs throughout ISM development in order to better understand the molecular mechanisms that mediate atrophy and death. Atrophy involves enhanced protein catabolism and reduced expression of the genes involved in respiration, adhesion and the contractile apparatus. In contrast, PCD involved the induction of numerous proteases, DNA methylases, membrane transporters, ribosomes, and anaerobic metabolism. These changes in gene expression are largely repressed when insects are injected with the insect steroid hormone 20-hydroxyecdysone, which delays death. The expression of the death-associated proteins may be greatly enhanced by reductions in specific microRNAs that function to repress translation. This study not only provides fundamental new insights into basic developmental processes, it may also represent a powerful resource for identifying potential diagnostic markers and molecular targets for therapeutic intervention.

中文翻译：

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骨骼肌萎缩和程序性细胞死亡期间差异基因表达的高分辨率分析。

骨骼肌在发育过程中或在应对各种损伤（包括不动、恶病质和脊髓损伤）时会发生萎缩和/或程序性细胞死亡 (PCD)。然而，萎缩的长期性质和组织内多种细胞类型的存在使分子分析复杂化。一种不受这些限制的模型是烟草天蛾 Manduca sexta 的节间肌肉 (ISM)。在变态结束时成虫羽化（羽化）前三天，ISM 启动非病理性萎缩程序，导致质量减少 40%。然后 ISM 产生羽化行为并在接下来的 30 小时内启动非凋亡 PCD。我们对整个 ISM 开发过程中的所有 mRNA 和 microRNA 进行了全面的转录组学分析，以更好地了解介导萎缩和死亡的分子机制。萎缩涉及增强的蛋白质分解代谢和参与呼吸、粘附和收缩装置的基因表达减少。相比之下，PCD 涉及多种蛋白酶、DNA 甲基化酶、膜转运蛋白、核糖体和厌氧代谢的诱导。当昆虫注射昆虫类固醇激素 20-羟基蜕皮激素时，基因表达的这些变化在很大程度上被抑制，从而延迟死亡。通过减少具有抑制翻译功能的特定微 RNA，可以大大增强死亡相关蛋白的表达。