骨骼肌中核质信号的年龄依赖性变化。
Age-dependent changes in nuclear-cytoplasmic signaling in skeletal muscle.
作者信息
Iyer Shama R, Hsia Ru-Ching, Folker Eric S, Lovering Richard M
机构信息
Departments of Orthopaedics, University of Maryland School of Medicine, USA.
Core Imaging Facility, University of Maryland Dental School, USA.
出版信息
Exp Gerontol. 2021 Jul 15;150:111338. doi: 10.1016/j.exger.2021.111338. Epub 2021 Apr 17.
UNLABELLED
Mechanical forces are conducted through myofibers and into nuclei to regulate muscle development, hypertrophy, and homeostasis. We hypothesized that nuclei in aged muscle have changes in the nuclear envelope and associated proteins, resulting in altered markers of mechano-signaling.
METHODS
YAP/TAZ protein expression and gene expression of downstream targets, Ankrd1 and Cyr61, were evaluated as mechanotransduction indicators. Expression of proteins in the nuclear lamina and the nuclear pore complex (NPC) were assessed, and nuclear morphology was characterized by electron microscopy. Nuclear envelope permeability was assessed by uptake of 70 kDa fluorescent dextran.
RESULTS
Nuclear changes with aging included a relative decrease of lamin β1 and Nup107, and a relative increase in Nup93, which could underlie the aberrant nuclear morphology, increased nuclear leakiness, and elevated YAP/TAZ signaling.
CONCLUSION
Aged muscles have hyperactive nuclear-cytoplasmic signaling, indicative of altered nuclear mechanotransduction. These data highlight a possible role for the nucleus in aging-related aberrant mechano-sensing.
未标记
机械力通过肌纤维传导至细胞核，以调节肌肉发育、肥大和内环境稳定。我们假设衰老肌肉中的细胞核在核膜及相关蛋白方面存在变化，从而导致机械信号标记物改变。
方法
评估YAP/TAZ蛋白表达以及下游靶点Ankrd1和Cyr61的基因表达，作为机械转导指标。评估核纤层和核孔复合体（NPC）中蛋白质的表达，并通过电子显微镜对核形态进行表征。通过70 kDa荧光葡聚糖的摄取评估核膜通透性。
结果
随着衰老，细胞核变化包括核纤层蛋白β1和Nup107相对减少，Nup93相对增加，这可能是异常核形态、核渗漏增加以及YAP/TAZ信号升高的基础。
结论
衰老肌肉具有活跃的核质信号传导，表明核机械转导发生改变。这些数据突出了细胞核在衰老相关异常机械传感中的可能作用。
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