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FTO抑制剂大黄酸抑制成肌细胞分化并延缓骨骼肌再生

Inhibitor of FTO, Rhein, Restrains the Differentiation of Myoblasts and Delays Skeletal Muscle Regeneration.

作者信息

Li Rongyang, Cao Yan, Wu Wangjun, Liu Honglin, Xu Shiyong

机构信息

College of Animal Science and Food Engineering, Jinling Institute of Technology, Nanjing 210095, China.

Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.

出版信息

Animals (Basel). 2024 Aug 22;14(16):2434. doi: 10.3390/ani14162434.

DOI:10.3390/ani14162434
PMID:39199967
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11350746/
Abstract

N6-methyladenosine (m6A) is a crucial RNA modification affecting skeletal muscle development. Rhein, an anti-inflammatory extract, inhibits , a key demethylase in m6A metabolism. Our study showed that during muscle fiber formation, and expression increased while m6A levels decreased. After muscle injury, and expression initially rose but later fell, while m6A levels initially dropped and then recovered. Inhibition of by Rhein reduced MyHC and expression, indicating myoblast differentiation suppression. In a mouse model, Rhein decreased MyHC expression and muscle fiber cross-sectional area, delaying muscle regeneration. Rhein's ability to increase RNA m6A modification delays skeletal muscle remodeling post-injury, suggesting a new medicinal application for this plant extract.

摘要

N6-甲基腺苷(m6A)是一种影响骨骼肌发育的关键RNA修饰。大黄酸是一种抗炎提取物,可抑制m6A代谢中的关键去甲基化酶。我们的研究表明,在肌纤维形成过程中,该去甲基化酶的表达增加而m6A水平降低。肌肉损伤后,该去甲基化酶的表达最初上升但随后下降,而m6A水平最初下降然后恢复。大黄酸对该去甲基化酶的抑制作用降低了肌球蛋白重链(MyHC)和其他相关蛋白的表达,表明成肌细胞分化受到抑制。在小鼠模型中,大黄酸降低了MyHC表达和肌纤维横截面积,延缓了肌肉再生。大黄酸增加RNA m6A修饰的能力延迟了损伤后骨骼肌的重塑,提示这种植物提取物有新的药用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6888/11350746/41fcd199ea91/animals-14-02434-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6888/11350746/fe013a42063d/animals-14-02434-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6888/11350746/419bc2d56430/animals-14-02434-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6888/11350746/ca1d75282ec7/animals-14-02434-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6888/11350746/9750547d9596/animals-14-02434-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6888/11350746/41fcd199ea91/animals-14-02434-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6888/11350746/fe013a42063d/animals-14-02434-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6888/11350746/419bc2d56430/animals-14-02434-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6888/11350746/ca1d75282ec7/animals-14-02434-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6888/11350746/9750547d9596/animals-14-02434-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6888/11350746/41fcd199ea91/animals-14-02434-g005.jpg

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本文引用的文献

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m6A echoes with DNA methylation: Coordinated DNA methylation and gene expression data analysis identified critical m6A genes associated with asthma.m6A 与 DNA 甲基化相互呼应:协调的 DNA 甲基化和基因表达数据分析确定了与哮喘相关的关键 m6A 基因。
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m A demethylase ALKBH5 drives denervation-induced muscle atrophy by targeting HDAC4 to activate FoxO3 signalling.去甲基酶 ALKBH5 通过靶向 HDAC4 激活 FoxO3 信号转导,从而促进失神经诱导的肌肉萎缩。
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Fusaric acid induces hepatic global m6A RNA methylation and differential expression of m6A regulatory genes - a pilot study.
Fusaric 酸诱导肝内全局 m6A RNA 甲基化和 m6A 调控基因的差异表达——一项初步研究。
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FTO-mediated demethylation of GADD45B promotes myogenesis through the activation of p38 MAPK pathway.FTO介导的GADD45B去甲基化通过激活p38丝裂原活化蛋白激酶(MAPK)途径促进肌生成。
Mol Ther Nucleic Acids. 2021 Jun 24;26:34-48. doi: 10.1016/j.omtn.2021.06.013. eCollection 2021 Dec 3.
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Genetic drivers of mA methylation in human brain, lung, heart and muscle.人类大脑、肺、心脏和肌肉中 mA 甲基化的遗传驱动因素。
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Regulation of RNA N-methyladenosine modification and its emerging roles in skeletal muscle development.RNA N6-甲基腺苷修饰的调控及其在骨骼肌发育中的新兴作用。
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