Early Growth Response 3 (Egr3) Contributes a Maintenance of C2C12 Myoblast Proliferation
Early Growth Response 3 (Egr3) Contributes a Maintenance of C2C12 Myoblast Proliferation
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DOI：
10.1002/jcp.25574
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发表时间：
2017-05-01
影响因子：
5.6
通讯作者：
Akema, Tatsuo
中科院分区：
文献类型：
--
作者：
Kurosaka, Mitsutoshi;Ogura, Yuji;Akema, Tatsuo
卫星细胞增殖是成体肌肉发生的重要过程。然而，它的调控机制仍不清楚。早期生长反应3(Egr3)是一种锌指转录因子，调节不同的细胞功能。据报道，Egr3与多个信号分子相互作用，这些信号分子也是已知的调节卫星细胞增殖的分子。因此，Egr3可能参与了卫星细胞的增殖。这项研究的结果表明，心脏毒素损伤后再生的小鼠骨骼肌中Egr3转录水平上调。利用C2C12成肌细胞培养(一种激活的卫星细胞模型)，结果表明shRNA抑制Egr3会损害成肌细胞的增殖率。结果还表明，在Egr3抑制的细胞中，核因子-kappaB的转录活性降低。Egr3的抑制与Annexin V+细胞比例和caspase-3、caspase-7、Poly-ADP核糖聚合酶等凋亡蛋白活性的增加有关。而PAN-caspase抑制剂Z-VAD-FMK可部分恢复抑制Egr3对细胞增殖的抑制作用。综上所述，这些结果表明Egr3通过与生存信号的相互作用参与成肌细胞的增殖。(C)2016威利期刊公司。
Satellite cell proliferation is a crucially important process for adult myogenesis. However, its regulatory mechanisms remain unknown. Early growth response 3 (Egr3) is a zinc-finger transcription factor that regulates different cellular functions. Reportedly, Egr3 interacts with multiple signaling molecules that are also known to regulate satellite cell proliferation. Therefore, it is possible that Egr3 is involved in satellite cell proliferation. Results of this study have demonstrated that Egr3 transcript levels are upregulated in regenerating mouse skeletal muscle after cardiotoxin injury. Using C2C12 myoblast culture (a model of activated satellite cells), results show that inhibition of Egr3 by shRNA impairs the myoblast proliferation rate. Results also show reduction of NF-kappa B transcriptional activity in Egr3-inhibited cells. Inhibition of Egr3 is associated with an increase in annexin V+ cell fraction and apoptotic protein activity including caspase-3 and caspase-7, and Poly-ADP ribose polymerase. By contrast, the reduction of cellular proliferation by inhibition of Egr3 was partially recovered by treatment of pan-caspase inhibitor Z-VAD-FMK. Collectively, these results suggest that Egr3 is involved in myoblast proliferation by interaction with survival signaling. (C) 2016 Wiley Periodicals, Inc.