Division of Regenerative Medical Engineering, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan.
Am J Physiol Cell Physiol. 2013 Mar;304(6):C541-7. doi: 10.1152/ajpcell.00243.2012. Epub 2013 Jan 16.
Mammalian skeletal muscles undergo adaptation in response to changes in the functional demands upon them, involving mechanical-stress-induced cellular signaling called "mechanotransduction." We hypothesized that p130Cas, which is reported to act as a mechanosensor that transduces mechanical extension into cellular signaling, plays an important role in maintaining and promoting skeletal muscle adaptation in response to mechanical stress via the p38 MAPK signaling pathway. We demonstrate that muscle-specific p130Cas-/- mice express the contractile proteins normally in skeletal muscle. Furthermore, muscle-specific p130Cas-/- mice show normal mechanical-stress-induced muscle adaptation, including exercise-induced IIb-to-IIa muscle fiber type transformation and hypertrophy. Finally, we provide evidence that exercise-induced p38 MAPK signaling is not impaired by the muscle-specific deletion of p130Cas. We conclude that p130Cas plays a limited role in mechanical-stress-induced skeletal muscle adaptation.
哺乳动物的骨骼肌会根据功能需求的变化而发生适应性改变,这涉及到一种被称为“机械转导”的机械应激诱导的细胞信号转导。我们假设 p130Cas 作为一种机械感受器,将机械伸展转化为细胞信号转导,通过 p38 MAPK 信号通路在维持和促进骨骼肌对机械应激的适应中发挥重要作用。我们证明,肌肉特异性 p130Cas-/- 小鼠在骨骼肌中正常表达收缩蛋白。此外,肌肉特异性 p130Cas-/- 小鼠表现出正常的机械应激诱导的肌肉适应性改变,包括运动诱导的 IIb 型向 IIa 型肌纤维类型转变和肥大。最后,我们提供的证据表明,肌肉特异性敲除 p130Cas 不会损害运动诱导的 p38 MAPK 信号转导。我们的结论是,p130Cas 在机械应激诱导的骨骼肌适应性改变中发挥有限的作用。