Satellite cell depletion does not affect diaphragm adaptations to hypoxia.
Satellite cell depletion does not affect diaphragm adaptations to hypoxia.
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卫星细胞耗竭不会影响膈肌对缺氧的适应。
DOI：
10.1152/japplphysiol.00083.2022
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Dupont-Versteegden,EstherE
中科院分区：
文献类型：
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作者：
Thomas,NicholasT;Confides,AmyL;Fry,ChristopherS;Dupont-Versteegden,EstherE
膈肌是负责吸气的主要骨骼肌，容易受到与年龄相关的功能和形态下降的影响。膈肌中的卫星细胞在一生中都会融合成不受干扰的肌纤维，但它们在适应膈肌缺氧中的作用尚不清楚。鉴于它们的持续融合，我们假设卫星细胞耗竭将对膈肌缺氧的适应产生负面影响，特别是随着衰老。我们使用可诱导卫星细胞耗竭的 Pax7CreER/CreER:R26RDTA/DTA 遗传小鼠模型来研究成年（6 个月）和老年（22 个月）雄性小鼠的膈肌对缺氧的反应。小鼠接受10% FIO2 常压缺氧或常氧4周。我们发现，卫星细胞耗竭对成年或老年小鼠的膈肌纤维横截面积、纤维类型分布、肌核密度或细胞外基质的调节没有影响。此外，我们发现，随着缺氧和年龄（主要影响），肌纤维横截面积降低，而隔膜中的细胞外基质含量随着年龄（主要影响）的增加而增加，卫星细胞丰度降低。最后，在卫星细胞耗尽的小鼠的膈肌中观察到更多数量的 Pax3-mRNA+ 细胞，与缺氧无关（主要效应），这可能是卫星细胞损失的补偿机制。我们得出的结论是，无论是成年还是老年小鼠，膈肌适应缺氧都不需要卫星细胞。新的和值得注意的卫星细胞在整个生命过程中表现出与膈肌纤维的一致融合，这表明在维持体内平衡方面发挥着关键作用。在这里，我们报告了成年和老年小鼠在有和没有卫星细胞的情况下膈肌对缺氧的适应相同。此外，我们提出卫星细胞耗尽的膈肌中较高数量的 Pax3 阳性细胞可作为一种补偿机制。
The diaphragm is the main skeletal muscle responsible for inspiration and is susceptible to age-associated decline in function and morphology. Satellite cells in diaphragm fuse into unperturbed muscle fibers throughout life, yet their role in adaptations to hypoxia in diaphragm is unknown. Given their continual fusion, we hypothesize that satellite cell depletion will negatively impact adaptations to hypoxia in the diaphragm, particularly with aging. We used the Pax7CreER/CreER:R26RDTA/DTAgenetic mouse model of inducible satellite cell depletion to investigate diaphragm responses to hypoxia in adult (6 mo) and aged (22 mo) male mice. The mice were subjected to normobaric hypoxia at 10% FIO2 or normoxia for 4 wk. We showed that satellite cell depletion had no effect on diaphragm muscle fiber cross-sectional area, fiber-type distribution, myonuclear density, or regulation of extracellular matrix in either adult or aged mice. Furthermore, we showed lower muscle fiber cross-sectional area with hypoxia and age (main effects), while extracellular matrix content was higher and satellite cell abundance was lower with age (main effect) in diaphragm. Lastly, a greater number of Pax3-mRNA+cells was observed in diaphragm muscle of satellite cell-depleted mice independent of hypoxia (main effect), potentially as a compensatory mechanism for the loss of satellite cells. We conclude that satellite cells are not required for diaphragm muscle adaptations to hypoxia in either adult or aged mice.NEW & NOTEWORTHYSatellite cells show consistent fusion into diaphragm muscle fibers throughout life, suggesting a critical role in maintaining homeostasis. Here, we report identical diaphragm adaptations to hypoxia with and without satellite cells in adult and aged mice. In addition, we propose that the higher number of Pax3-positive cells in satellite cell-depleted diaphragm muscle acts as a compensatory mechanism.