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肌细胞增强因子 2A 通过肌浆球蛋白 2 促进牛骨骼肌成肌细胞的增殖,其抑制作用可减弱成肌分化。

Myocyte enhancer factor 2A promotes proliferation and its inhibition attenuates myogenic differentiation via myozenin 2 in bovine skeletal muscle myoblast.

机构信息

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.

National Beef Cattle Improvement Center in China, Yangling, Shaanxi, P. R. China.

出版信息

PLoS One. 2018 Apr 26;13(4):e0196255. doi: 10.1371/journal.pone.0196255. eCollection 2018.

DOI:10.1371/journal.pone.0196255
PMID:29698438
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5919640/
Abstract

Myocyte enhancer factor 2A (MEF2A) is widely distributed in various tissues or organs and plays crucial roles in multiple biological processes. To examine the potential effects of MEF2A on skeletal muscle myoblast, the functional role of MFE2A in myoblast proliferation and differentiation was investigated. In this study, we found that the mRNA expression level of Mef2a was dramatically increased during the myogenesis of bovine skeletal muscle primary myoblast. Overexpression of MEF2A significantly promoted myoblast proliferation, while knockdown of MEF2A inhibited the proliferation and differentiation of myoblast. RT-PCR and western blot analysis revealed that this positive effect of MEF2A on the proliferation of myoblast was carried out by triggering cell cycle progression by activating CDK2 protein expression. Besides, MEF2A was found to be an important transcription factor that bound to the myozenin 2 (MyoZ2) proximal promoter and performed upstream of MyoZ2 during myoblast differentiation. This study provides the first experimental evidence that MEF2A is a positive regulator in skeletal muscle myoblast proliferation and suggests that MEF2A regulates myoblast differentiation via regulating MyoZ2.

摘要

肌细胞增强因子 2A(MEF2A)广泛分布于各种组织或器官中,在多种生物过程中发挥关键作用。为了研究 MEF2A 对骨骼肌成肌细胞的潜在影响,研究了 MEF2A 在成肌细胞增殖和分化中的功能作用。在这项研究中,我们发现 Mef2a 的 mRNA 表达水平在牛骨骼肌原代成肌细胞的肌发生过程中显著增加。MEF2A 的过表达显著促进成肌细胞增殖,而 MEF2A 的敲低则抑制成肌细胞的增殖和分化。RT-PCR 和 Western blot 分析表明,MEF2A 通过激活 CDK2 蛋白表达来触发细胞周期进程,从而对成肌细胞的增殖产生这种正向作用。此外,还发现 MEF2A 是一种重要的转录因子,它与肌联蛋白 2(MyoZ2)近端启动子结合,并在成肌细胞分化过程中位于 MyoZ2 的上游。这项研究首次提供了实验证据,证明 MEF2A 是骨骼肌成肌细胞增殖的正向调节剂,并表明 MEF2A 通过调节 MyoZ2 来调节成肌细胞分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac8/5919640/24d706984fc1/pone.0196255.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac8/5919640/cd20517ad85b/pone.0196255.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac8/5919640/e09f874e33a8/pone.0196255.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac8/5919640/c13079967151/pone.0196255.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac8/5919640/ef63676abeee/pone.0196255.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac8/5919640/49a791cc3a7e/pone.0196255.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac8/5919640/24d706984fc1/pone.0196255.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac8/5919640/cd20517ad85b/pone.0196255.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac8/5919640/e09f874e33a8/pone.0196255.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac8/5919640/c13079967151/pone.0196255.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac8/5919640/ef63676abeee/pone.0196255.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac8/5919640/49a791cc3a7e/pone.0196255.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac8/5919640/24d706984fc1/pone.0196255.g006.jpg

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