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通过抑制增殖和促进凋亡的 p53 通路抑制 C2C12 成肌发生。

Suppresses C2C12 Myogenic Development by Inhibiting Proliferation and Promoting Apoptosis via the p53 Pathway.

机构信息

National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.

Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, 1955 East-West Road, Honolulu, HI 96822, USA.

出版信息

Cells. 2019 Aug 23;8(9):959. doi: 10.3390/cells8090959.

DOI:10.3390/cells8090959
PMID:31450751
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6770762/
Abstract

Skeletal muscle plays a crucial role in physical activity and in regulating body energy and protein balance. Myoblast proliferation, differentiation, and apoptosis are indispensable processes for myoblast myogenesis. Profilin 2a (PFN2a) is a ubiquitous actin monomer-binding protein and promotes lung cancer growth and metastasis through suppressing the nuclear localization of histone deacetylase 1 (HDAC1). However, how regulates myoblast myogenic development is still not clear. We constructed a C2C12 mouse myoblast cell line overexpressing . The CRISPR/Cas9 system was used to study the function of in C2C12 myogenic development. We find that suppresses proliferation and promotes apoptosis and consequentially downregulates C2C12 myogenic development. The suppression of also decreases the amount of HDAC1 in the nucleus and increases the protein level of p53 during C2C12 myogenic development. Therefore, we propose that suppresses C2C12 myogenic development via the p53 pathway. Si- (siRNA-) reverses the inhibitory effect on C2C12 proliferation and the promotion effect on C2C12 apoptosis, and then attenuates the suppression of on myogenic differentiation. Our results expand understanding of regulatory mechanisms in myogenic development and suggest potential therapeutic targets for muscle atrophy-related diseases.

摘要

骨骼肌在身体活动和调节身体能量和蛋白质平衡中起着至关重要的作用。成肌细胞的增殖、分化和凋亡是成肌细胞生成的必不可少的过程。 Profilin 2a (PFN2a) 是一种普遍存在的肌动蛋白单体结合蛋白，通过抑制组蛋白去乙酰化酶 1 (HDAC1) 的核定位来促进肺癌的生长和转移。然而， 如何调节成肌细胞的成肌发育仍不清楚。我们构建了一个过表达 的 C2C12 小鼠成肌细胞系。CRISPR/Cas9 系统用于研究 在 C2C12 成肌发育中的功能。我们发现 抑制增殖并促进凋亡，从而下调 C2C12 成肌发育。 的抑制还减少了细胞核中 HDAC1 的数量，并增加了 C2C12 成肌发育过程中的 p53 蛋白水平。因此，我们提出 通过 p53 途径抑制 C2C12 成肌发育。Si- (siRNA-) 逆转了 对 C2C12 增殖的抑制作用和对 C2C12 凋亡的促进作用，从而减弱了 对成肌分化的抑制作用。我们的研究结果扩展了对 调节成肌发育机制的理解，并为与肌肉萎缩相关的疾病提供了潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/17a51f1ce8bb/cells-08-00959-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/c4f156d0f420/cells-08-00959-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/7057ec9b35b0/cells-08-00959-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/0e69c7ef103b/cells-08-00959-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/4e2b1d53e2fd/cells-08-00959-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/4706c3830550/cells-08-00959-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/401422bcd082/cells-08-00959-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/17a51f1ce8bb/cells-08-00959-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/c4f156d0f420/cells-08-00959-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/7057ec9b35b0/cells-08-00959-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/0e69c7ef103b/cells-08-00959-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/4e2b1d53e2fd/cells-08-00959-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/4706c3830550/cells-08-00959-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/401422bcd082/cells-08-00959-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/6770762/17a51f1ce8bb/cells-08-00959-g007.jpg

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