Mendias Christopher L, Schwartz Andrew J, Grekin Jeremy A, Gumucio Jonathan P, Sugg Kristoffer B
Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan;
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan; and.
J Appl Physiol (1985). 2017 Mar 1;122(3):571-579. doi: 10.1152/japplphysiol.00719.2016. Epub 2016 Dec 15.
Skeletal muscle can adapt to increased mechanical loads by undergoing hypertrophy. Transient reductions in whole muscle force production have been reported during the onset of hypertrophy, but contractile changes in individual muscle fibers have not been previously studied. Additionally, the extracellular matrix (ECM) stores and transmits forces from muscle fibers to tendons and bones, and determining how the ECM changes during hypertrophy is important in understanding the adaptation of muscle tissue to mechanical loading. Using the synergist ablation model, we sought to measure changes in muscle fiber contractility, collagen content, and cross-linking, and in the expression of several genes and activation of signaling proteins that regulate critical components of myogenesis and ECM synthesis and remodeling during muscle hypertrophy. Tissues were harvested 3, 7, and 28 days after induction of hypertrophy, and nonoverloaded rats served as controls. Muscle fiber specific force (sF), which is the maximum isometric force normalized to cross-sectional area, was reduced 3 and 7 days after the onset of mechanical overload, but returned to control levels by 28 days. Collagen abundance displayed a similar pattern of change. Nearly a quarter of the transcriptome changed over the course of overload, as well as the activation of signaling pathways related to hypertrophy and atrophy. Overall, this study provides insight into fundamental mechanisms of muscle and ECM growth, and indicates that although muscle fibers appear to have completed remodeling and regeneration 1 mo after synergist ablation, the ECM continues to be actively remodeling at this time point. This study utilized a rat synergist ablation model to integrate changes in single muscle fiber contractility, extracellular matrix composition, activation of important signaling pathways in muscle adaption, and corresponding changes in the muscle transcriptome to provide novel insight into the basic biological mechanisms of muscle fiber hypertrophy.
骨骼肌可通过肥大来适应增加的机械负荷。据报道，在肥大开始时，整块肌肉的力量产生会出现短暂下降，但此前尚未对单个肌纤维的收缩变化进行研究。此外，细胞外基质（ECM）储存并将力量从肌纤维传递至肌腱和骨骼，确定肥大过程中ECM的变化对于理解肌肉组织对机械负荷的适应至关重要。利用协同肌切除模型，我们试图测量肌纤维收缩性、胶原蛋白含量和交联的变化，以及几种基因的表达和信号蛋白的激活情况，这些基因和信号蛋白在肌肉肥大过程中调节肌生成以及ECM合成与重塑的关键成分。在诱导肥大后的第3、7和28天采集组织，未过载的大鼠作为对照。肌纤维比力（sF），即归一化至横截面积的最大等长力，在机械过载开始后的第3天和第7天降低，但到第28天时恢复到对照水平。胶原蛋白丰度呈现出类似的变化模式。在过载过程中，近四分之一的转录组发生了变化，与肥大和萎缩相关的信号通路也被激活。总体而言，本研究深入了解了肌肉和ECM生长的基本机制，并表明尽管在协同肌切除1个月后肌纤维似乎已完成重塑和再生，但此时ECM仍在积极重塑。本研究利用大鼠协同肌切除模型，整合了单个肌纤维收缩性的变化、细胞外基质组成、肌肉适应过程中重要信号通路的激活以及肌肉转录组的相应变化，以提供对肌纤维肥大基本生物学机制的新见解。
