Attenuation of p38-mediated miR-1/133 expression facilitates myoblast proliferation during the early stage of muscle regeneration.
Attenuation of p38-mediated miR-1/133 expression facilitates myoblast proliferation during the early stage of muscle regeneration.
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p38 介导的 miR-1/133 表达减弱促进肌肉再生早期阶段的成肌细胞增殖
DOI：
10.1371/journal.pone.0041478
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ying H
中科院分区：
文献类型：
--
作者：
Zhang D;Li X;Chen C;Li Y;Zhao L;Jing Y;Liu W;Wang X;Zhang Y;Xia H;Chang Y;Gao X;Yan J;Ying H
肌外伤后成肌细胞增殖受多种因素调控，包括生长因子、信号通路、转录因子和mirna。然而，这些调控因子背后的分子机制仍不清楚。在这里，我们发现p38信号是miR-1/133a簇转录所必需的，在各种动物模型中，p38活性和miR-1/133表达在肌肉再生的早期阶段都有所减弱。此外，我们发现miR-1和miR-133都通过诱导G1期阻滞来降低Cyclin D1的表达并抑制成肌细胞的增殖。此外，我们证明miR-133通过靶向Sp1抑制有丝分裂进程，Sp1介导Cyclin D1转录，而miR-1通过靶向Cyclin D1抑制G1/S阶段转变。最后，我们发现在肌肉再生过程中升高的促增殖性FGF2会减弱p38信号和miR-1/133的表达。综上所述，我们的研究结果表明，FGF2下调p38介导的miR-1/133表达，随后上调Sp1/Cyclin D1，有助于肌肉再生早期成肌细胞增殖的增加。
Myoblast proliferation following myotrauma is regulated by multiple factors including growth factors, signal pathways, transcription factors, and miRNAs. However, the molecular mechanisms underlying the orchestration of these regulatory factors remain unclear. Here we show that p38 signaling is required for miR-1/133a clusters transcription and both p38 activity and miR-1/133 expression are attenuated during the early stage of muscle regeneration in various animal models. Additionally, we show that both miR-1 and miR-133 reduce Cyclin D1 expression and repress myoblast proliferation by inducing G1 phase arrest. Furthermore, we demonstrate that miR-133 inhibits mitotic progression by targeting Sp1, which mediates Cyclin D1 transcription, while miR-1 suppresses G1/S phase transition by targeting Cyclin D1. Finally, we reveal that proproliferative FGF2, which is elevated during muscle regeneration, attenuates p38 signaling and miR-1/133 expression. Taken together, our results suggest that downregulation of p38-mediated miR-1/133 expression by FGF2 and subsequent upregulation of Sp1/Cyclin D1 contribute to the increased myoblast proliferation during the early stage of muscle regeneration.
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影响因子：
56.9
作者：
DIMARIO, J;BUFFINGER, N;STROHMAN, RC
通讯作者：
STROHMAN, RC
影响因子：
30.8
作者：
Hui, Lijian;Bakiri, Latifa;Wagner, Erwin F.
通讯作者：
Wagner, Erwin F.
DOI：
10.1046/j.1439-0264.2003.00439.x
发表时间：
2003-02-01
期刊：
ANATOMIA HISTOLOGIA EMBRYOLOGIA-JOURNAL OF VETERINARY MEDICINE SERIES C
影响因子：
--
作者：
Çalgüner, E;Gözil, R;Sabuncuoglu, H
通讯作者：
Sabuncuoglu, H
DOI：
10.1083/jcb.200911036
发表时间：
2010-09-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen JF;Tao Y;Li J;Deng Z;Yan Z;Xiao X;Wang DZ
通讯作者：
Wang DZ
影响因子：
2.5
作者：
Lefaucheur, JP;Sebille, A
通讯作者：
Sebille, A