Age-related decrease in muscle satellite cells is accompanied with diminished expression of early growth response 3 in mice

Age-related decrease in muscle satellite cells is accompanied with diminished expression of early growth response 3 in mice
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小鼠中与年龄相关的肌肉卫星细胞减少伴随着早期生长反应 3 表达的减少

DOI:
10.1007/s11033-019-05189-5
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发表时间:
2020
期刊:
Mol. Biol. Rep.
影响因子:
--
通讯作者:
Funabashi T.
Funabashi T.
中科院分区:
--
文献类型:
--
作者:
Ogura Y.;Sato S.;Kurosaka M.;Kotani T.;Fujiya H.;Funabashi T.

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骨骼肌再生主要依赖于肌卫星细胞。正常的肌肉再生需要足够数量的卫星细胞。最近的研究表明,骨骼肌卫星细胞的数量随着年龄的增长而减少,导致老年人肌肉再生障碍。我们的前期研究表明,锌指转录因子早期生长反应3(Egr 3)在维持成肌细胞数量方面起着重要作用,提示肌卫星细胞的年龄相关性减少与Egr 3的表达水平有关。本研究的目的是研究衰老是否会改变Egr 3在卫星细胞中的表达。在本研究中检查了两组雄性C57 BL/6 J小鼠:年轻(3个月)和老年(17个月)。免疫组织化学染色显示,老年小鼠正常和损伤肌肉中卫星细胞数量减少。在荧光激活细胞分选分离的正常和受伤的肌肉卫星细胞中,Egr 3的mRNA表达随年龄的增长而显着下降,无论是否受伤。与这些结果相一致的是,来自老年小鼠的卫星细胞中Pax 7 mRNA水平也下降。另外,通过shRNA抑制Egr 3表达降低了培养的成肌细胞中Pax 7蛋白的表达。这些结果表明,Egr 3与老年人肌肉卫星细胞的年龄相关性下降有关。此外,Egr 3可能与Pax 7的调节有关。因此,Egr 3表达的丧失可能阐明了老年人MSC功能和肌肉再生的减弱。
Skeletal muscle regeneration is mostly dependent on muscle satellite cells. Proper muscle regeneration requires enough number of satellite cells. Recent studies have suggested that the number of satellite cells in skeletal muscle declines as we age, leading to the impairment of muscle regeneration in older population. Our earlier study demonstrated that zinc finger transcription factor early growth response 3 (Egr3) plays an important role for maintaining the number of myoblasts, suggesting that age-related decrease in muscle satellite cell should be associated with the expression levels of Egr3. The aim of this study was to investigate whether aging would alter the Egr3 expression in satellite cells. A couple groups of male C57BL/6J mice were examined in this study: young (3 Mo) and old (17 Mo). Immunohistochemical staining showed that the satellite cell number decreased in normal and injured muscles of old mice. In fluorescence-activated cell sorting-isolated muscle satellite cells from normal and injured muscles, the mRNA expression of Egr3 was significantly decreased with age regardless of injury. In harmony with these results, Pax7 mRNA levels also decreased in the satellite cells from old mice. Alternatively, inhibition of Egr3 expression by shRNA decreased Pax7 protein expression in cultured myoblasts. These results suggest that Egr3 is associated with the age-related decline of muscle satellite cells in older population. Also, Egr3 might be implicated in the regulation of Pax7. Therefore, the loss of Egr3 expression may elucidate attenuated MSCs function and muscle regeneration in older age.
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