Depletion of Pax7+ satellite cells does not affect diaphragm adaptations to running in young or aged mice.
Depletion of Pax7+ satellite cells does not affect diaphragm adaptations to running in young or aged mice.
复制标题
Pax7 卫星细胞的耗竭不会影响年轻或老年小鼠的隔膜对跑步的适应。
DOI：
10.1113/jp274611
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发表时间：
2017
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：
Murach,KevinA;Confides,AmyL;Ho,Angel;Jackson,JannaR;Ghazala,LinaS;Peterson,CharlotteA;Dupont-Versteegden,EstherE
关键点卫星细胞耗竭不影响年轻或老年小鼠对自主轮跑的横膈膜适应。（4月龄）对老年膈肌表型的影响最小（24个月）。横膈膜中延长的卫星细胞耗竭不会导致过度的细胞外基质积累，在年轻和老年小鼠中，卫星细胞耗竭后Pax 3 mRNA+细胞的上调表明Pax 3+细胞可以补偿Pax 7+细胞的损失。横膈膜中的卫星细胞。未来的研究应该集中在适应运动和衰老过程中横膈膜中Pax 3+细胞的作用。摘要与后肢肌肉相比，卫星细胞对无应力横膈膜的贡献更高，这可能归因于该肌肉的持续激活以驱动通气。卫星细胞耗竭是否对年轻和老年小鼠在应激条件下的膈肌定量和定性特征产生负面影响尚不清楚。因此，我们使用诱导型Pax 7 CreER-R26 RDTA模型，在存在和不存在Pax 7+卫星细胞的情况下，在年轻和老年小鼠中用长时间的跑步活动来挑战膈肌。在4月龄时对小鼠进行溶媒（Veh，卫星细胞充满）或他莫昔芬（Tam，卫星细胞耗尽）处理，然后在6月龄（幼龄）和22月龄（老龄）时让小鼠自愿跑步。年龄匹配、笼中饲养、Veh和Tam处理的小鼠（未使用滚轮）作为活动对照。分析了年轻（8个月）和老年（24个月）小鼠的膈肌。无论是否进行跑步活动，卫星细胞耗竭均未改变年轻或老年小鼠的膈肌平均纤维横截面积、纤维类型分布或细胞外基质含量。静止在vivo膈肌功能也不受卫星细胞耗竭。在年轻的卫星细胞耗尽的小鼠中，无论是否跑步，肌纤维密度都保持不变，尽管在没有卫星细胞的老年久坐（-7%）和跑步（-19%）小鼠中肌纤维密度适度降低（P< 0.05）。使用荧光原位杂交，我们在年轻和老年卫星细胞缺失的膈肌中检测到较高的Pax 3 mRNA+细胞密度（P< 0.05），这可能补偿了Pax 7+卫星细胞的损失。
Key pointsSatellite cell depletion does not affect diaphragm adaptations to voluntary wheel running in young or aged mice.Satellite cell depletion early in life (4 months of age) has minimal effect on diaphragm phenotype by old age (24 months).Prolonged satellite cell depletion in the diaphragm does not result in excessive extracellular matrix accumulation, in contrast to what has been reported in hind limb muscles.Up‐regulation of Pax3 mRNA+ cells after satellite cell depletion in young and aged mice suggests that Pax3+ cells may compensate for a loss of Pax7+ satellite cells in the diaphragm.Future investigations should focus on the role of Pax3+ cells in the diaphragm during adaptation to exercise and ageing.AbstractSatellite cell contribution to unstressed diaphragm is higher compared to hind limb muscles, which is probably attributable to constant activation of this muscle to drive ventilation. Whether satellite cell depletion negatively impacts diaphragm quantitative and qualitative characteristics under stressed conditions in young and aged mice is unknown. We therefore challenged the diaphragm with prolonged running activity in the presence and absence of Pax7+ satellite cells in young and aged mice using an inducible Pax7CreER‐R26RDTAmodel. Mice were vehicle (Veh, satellite cell‐replete) or tamoxifen (Tam, satellite cell‐depleted) treated at 4 months of age and were then allowed to run voluntarily at 6 months (young) and 22 months (aged). Age‐matched, cage‐dwelling, Veh‐ and Tam‐treated mice without wheel access served as activity controls. Diaphragm muscles were analysed from young (8 months) and aged (24 months) mice. Satellite cell depletion did not alter diaphragm mean fibre cross‐sectional area, fibre type distribution or extracellular matrix content in young or aged mice, regardless of running activity. Restingin vivodiaphragm function was also unaffected by satellite cell depletion. Myonuclear density was maintained in young satellite cell‐depleted mice regardless of running, although it was modestly reduced in aged sedentary (–7%) and running (–19%) mice without satellite cells (P< 0.05). Using fluorescencein situhybridization, we detected higher Pax3 mRNA+ cell density in both young and aged satellite cell‐depleted diaphragm muscle (P< 0.05), which may compensate for the loss of Pax7+ satellite cells.