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miR-18 抑制剂通过增加 MEF2D 表达促进牛骨骼肌卫星细胞的分化。

MiR-18 inhibitor promotes the differentiation of bovine skeletal muscle-derived satellite cells by increasing MEF2D expression.

机构信息

College of Life Science, Northeast Forestry University, Harbin, Heilongjiang 150040, China.

College of Life Science, Northeast Agriculture University, Harbin, Heilongjiang 150030, China.

出版信息

J Anim Sci. 2022 Nov 1;100(11). doi: 10.1093/jas/skac238.

Abstract

Skeletal muscle is composed of muscle fibers formed from myoblast differentiation. Recently, numerous researchers have demonstrated that microRNAs (miRNAs) play an essential role in modulating the proliferation and differentiation of myoblasts. Our previous study has shown that among the miR-17-92 cluster members, miR-17 and miR-20a together with miR-19b can efficiently promote the differentiation of murine C2C12 and bovine primary myoblasts. However, the role of miR-18 in this process remains elusive. In this study, we revealed that miR-18 inhibited the differentiation of bovine skeletal muscle-derived satellite cells (bMDSCs), whereas an miR-18 inhibitor significantly promoted cell differentiation (p < 0.001). Then, a target gene of miR-18 was found to be myocyte enhancer factor 2D (MEF2D), which is critical for myoblast differentiation. Furthermore, we found that the combination of the miR-18 inhibitor and miR-19 significantly improved the formation of bMDSCs-derived muscle fibers (p < 0.001). This study revealed the role of miR-18 in bovine skeletal muscle differentiation and contributed to the understanding of the regulatory mechanism of mammalian myogenic differentiation.

摘要

骨骼肌由肌母细胞分化形成的肌纤维组成。最近,许多研究人员已经证明,microRNAs(miRNAs)在调节肌母细胞的增殖和分化中起着至关重要的作用。我们之前的研究表明,在 miR-17-92 簇成员中,miR-17 和 miR-20a 与 miR-19b 一起可以有效地促进鼠 C2C12 和牛原代肌母细胞的分化。然而,miR-18 在这个过程中的作用仍不清楚。在这项研究中,我们揭示了 miR-18 抑制牛骨骼肌卫星细胞(bMDSCs)的分化,而 miR-18 抑制剂则显著促进细胞分化(p<0.001)。然后,发现 miR-18 的一个靶基因是肌细胞增强因子 2D(MEF2D),它对肌母细胞分化至关重要。此外,我们发现 miR-18 抑制剂和 miR-19 的组合显著改善了 bMDSCs 衍生的肌纤维的形成(p<0.001)。这项研究揭示了 miR-18 在牛骨骼肌分化中的作用,有助于理解哺乳动物成肌分化的调控机制。

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Cell Mol Life Sci. 2019 Dec;76(24):5041-5054. doi: 10.1007/s00018-019-03165-7. Epub 2019 Jun 18.
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Skeletal muscle mass is controlled by the MRF4-MEF2 axis.骨骼肌质量受 MRF4-MEF2 轴的控制。
Curr Opin Clin Nutr Metab Care. 2018 May;21(3):164-167. doi: 10.1097/MCO.0000000000000456.
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