Department of Animal Science, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
Nutrients. 2022 Apr 29;14(9):1861. doi: 10.3390/nu14091861.
Skeletal muscle atrophy is a complex degenerative disease characterized by decreased skeletal muscle mass, skeletal muscle strength, and function. MicroRNAs (miRNAs) are a potential therapeutic target, and natural products that regulate miRNA expression may be a safe and effective treatment strategy for muscle atrophy. Previous studies have shown beneficial effects of genistein treatment on muscle mass and muscle atrophy, but the mechanism is not fully understood. Differential co-expression network analysis revealed that miR-222 was upregulated in multiple skeletal muscle atrophy models. Subsequent in vitro (C2C12 myoblasts) and in vivo (C57BL/6 mice) experiments showed that genistein could alleviate dexamethasone-induced muscle atrophy and downregulate the expression of miR-222 in muscle tissue and C2C12 myotubes. The dual-luciferase reporter assay system confirmed that is a target gene of miR-222 and is regulated by genistein. In C2C12 myotubes, both dexamethasone and miR-222 overexpression promoted muscle atrophy, however, this function was significantly reduced after genistein treatment. Furthermore, we also observed that both genistein and miR-222 antagomiR could significantly inhibit dexamethasone-induced muscle atrophy in vivo. These results suggest that miR-222 may be involved in the regulation of genistein on muscle atrophy, and genistein and miR-222 may be used to improve muscle health.
骨骼肌萎缩是一种复杂的退行性疾病，其特征是骨骼肌质量、骨骼肌力量和功能下降。microRNAs（miRNAs）是一个有潜力的治疗靶点，调节 miRNA 表达的天然产物可能是肌肉萎缩的一种安全有效的治疗策略。先前的研究表明，染料木黄酮治疗对肌肉质量和肌肉萎缩有有益的影响，但机制尚不完全清楚。差异共表达网络分析表明，miR-222 在多种骨骼肌萎缩模型中上调。随后的体外（C2C12 成肌细胞）和体内（C57BL/6 小鼠）实验表明，染料木黄酮可以减轻地塞米松诱导的肌肉萎缩，并下调肌肉组织和 C2C12 肌管中 miR-222 的表达。双荧光素酶报告基因检测系统证实是 miR-222 的靶基因，并受染料木黄酮调节。在 C2C12 肌管中，地塞米松和 miR-222 过表达均促进肌肉萎缩，但经染料木黄酮处理后，这一功能明显减弱。此外，我们还观察到，染料木黄酮和 miR-222 拮抗 miRNA 均可显著抑制体内地塞米松诱导的肌肉萎缩。这些结果表明，miR-222 可能参与了染料木黄酮对肌肉萎缩的调节，染料木黄酮和 miR-222 可能被用于改善肌肉健康。
