Acetoacetate promotes muscle cell proliferation via the miR-133b/SRF axis through the Mek-Erk-MEF2 pathway.
Acetoacetate promotes muscle cell proliferation via the miR-133b/SRF axis through the Mek-Erk-MEF2 pathway.
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DOI：
10.1093/abbs/gmab079
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发表时间：
2021-06
影响因子：
3.7
通讯作者：
Ran Zhong;Renling Miao;Jiao Meng;Rimao Wu;Yong Zhang;Dahai Zhu
中科院分区：
文献类型：
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作者：
Ran Zhong;Renling Miao;Jiao Meng;Rimao Wu;Yong Zhang;Dahai Zhu
乙酰乙酸酯(AA)是一种重要的酮体，被用作氧化燃料，为包括大脑和骨骼肌在内的各种组织的细胞活动提供能量。我们最近揭示了AA的一个新的信号作用，表明它在体外促进肌肉细胞增殖，在体内促进肌肉再生，并改善MDX小鼠营养不良的肌肉表型。在这项研究中，我们对AA的这一功能提供了新的分子见解。我们发现AA通过转录上调肌肉特异性miR-133b的表达来促进C2C12细胞的增殖，进而通过靶向血清反应因子刺激肌肉细胞的增殖。此外，我们发现AA诱导的miR-133b的上调是由MEF2通过MEK-ERK1/2信号通路在转录上介导的。从机制上讲，我们的发现提供了进一步令人信服的证据，证明AA作为信号代谢物积极调节哺乳动物细胞中的各种细胞活动。
Acetoacetate (AA) is an important ketone body that is used as an oxidative fuel to supply energy for the cellular activities of various tissues, including the brain and skeletal muscle. We recently revealed a new signaling role for AA by showing that it promotes muscle cell proliferation in vitro, enhances muscle regeneration in vivo, and ameliorates the dystrophic muscle phenotype of Mdx mice. In this study, we provide new molecular insight into this function of AA. We show that AA promotes C2C12 cell proliferation by transcriptionally upregulating the expression of muscle-specific miR-133b, which in turn stimulates muscle cell proliferation by targeting serum response factor. Furthermore, we show that the AA-induced upregulation of miR-133b is transcriptionally mediated by MEF2 via the Mek-Erk1/2 signaling pathway. Mechanistically, our findings provide further convincing evidence that AA acts as signaling metabolite to actively regulate various cellular activities in mammalian cells.