Voluntary wheel running increases satellite cell abundance and improves recovery from disuse in gastrocnemius muscles from mice
Voluntary wheel running increases satellite cell abundance and improves recovery from disuse in gastrocnemius muscles from mice
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DOI：
10.1152/japplphysiol.00451.2017
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发表时间：
2018-06-01
影响因子：
3.3
通讯作者：
Alway, Stephen E.
中科院分区：
文献类型：
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作者：
Brooks, Matthew J.;Hajira, Ameena;Alway, Stephen E.
后肢悬吊去负荷后萎缩肌肉的再负荷可引起损伤并延长恢复时间。低冲击运动，如自愿轮跑，已被确定为啮齿动物的非损伤性康复治疗，但其对HSU后肌肉功能，形态和卫星细胞活性的影响尚不清楚。本研究验证了低冲击轮跑会增加卫星细胞增殖并改善HSU后小鼠肌肉结构和功能的恢复的假设。将年轻成年雄性和雌性C57 BL/6小鼠（n = 6/组）随机分成五组。这些包括HSU未恢复（HSU），HSU后14天正常行走恢复（HSU+NoWR），HSU后14天自愿车轮运行恢复（HSU+WR）。使用两个对照组：非悬挂小鼠笼对照组（Control）和自主轮跑对照组（ControlWR）。通过在小鼠的饮用水中提供5-溴-2 '-脱氧尿苷（BrdU）来评价卫星细胞活化。正如预期的那样，HSU显著降低了体内最大力，降低了体内疲劳性，并降低了跖屈肌中I型和IIa型肌球蛋白重链（MHC）的丰度。HSU+WR小鼠显著改善了跖屈肌的抗疲劳性，增加了I型和IIa型MHC的丰度，增加了纤维横截面积，并增加了腓肠肌中I型和IIA型肌纤维的百分比。与HSU + NoWR小鼠相比，HSU+WR小鼠肌纤维内BrdU阳性和Pax 7阳性细胞核的百分比也显著更高，MyoD与Pax 7蛋白的比例也更高。HSU后，机械转导蛋白Yes相关蛋白（雅普）随着再负荷而升高，但HSU + WR小鼠的无活性磷酸化雅普（丝氨酸127）水平较低，这可能有助于HSU后再负荷增加卫星细胞活化。这些结果表明，自主轮跑增加了HSU后的雅普信号传导和卫星细胞活性，这与恢复改善有关。本研究的数据表明，主动跑轮增加了卫星细胞活性，抑制了Yes相关蛋白（雅普）蛋白质相对于没有轮子运行，这与改善的肌肉恢复力，抗疲劳性，I型肌球蛋白重链的表达，以及废用后更大的纤维横截面积有关。
Reloading of atrophied muscles after hindlimb suspension unloading (HSU) can induce injury and prolong recovery. Low-impact exercise, such as voluntary wheel running, has been identified as a nondamaging rehabilitation therapy in rodents, but its effects on muscle function, morphology, and satellite cell activity after HSU are unclear. This study tested the hypothesis that low-impact wheel running would increase satellite cell proliferation and improve recovery of muscle structure and function after HSU in mice. Young adult male and female C57BL/6 mice (n = 6/group) were randomly placed into five groups. These included HSU without recovery (HSU), normal ambulatory recovery for 14 days after HSU (HSU+NoWR), and voluntary wheel running recovery for 14 days after HSU (HSU+WR). Two control groups were used: nonsuspended mouse cage controls (Control) and voluntary wheel running controls (ControlWR). Satellite cell activation was evaluated by providing mice 5-bromo-2 '-deoxyuridine (BrdU) in their drinking water. As expected, HSU significantly reduced in vivo maximal force, decreased in vivo fatigability, and decreased type I and IIa myosin heavy chain (MHC) abundance in plantarflexor muscles. HSU+WR mice significantly improved plantarflexor fatigue resistance, increased type I and IIa MHC abundance, increased fiber cross-sectional area, and increased the percentage of type I and IIA muscle fibers in the gastrocnemius muscle. HSU+WR mice also had a significantly greater percentage of BrdU-positive and Pax 7-positive nuclei inside muscle fibers and a greater MyoD-to-Pax 7 protein ratio compared with HSU + NoWR mice. The mechanotransduction protein Yes-associated protein (YAP) was elevated with reloading after HSU, but HSU + WR mice had lower levels of the inactive phosphorylaled YAP(serine127), which may have contributed to increased satellite cell activation with reloading after HSU. These results indicate that voluntary wheel running increased YAP signaling and satellite cell activity after HSU and this was associated with improved recovery.NEW & NOTEWORTHY Although satellite cell involvement in muscle remodeling has been challenged, the data in this study suggest that voluntary wheel running increased satellite cell activity and suppressed Yes-associated protein (YAP) protein relative to no wheel running and this was associated with improved muscle recovery of force, fatigue resistance, expression of type I myosin heavy chain, and greater fiber cross-sectional area after disuse.