Genistein Promotes Skeletal Muscle Regeneration by Regulating miR-221/222.

Genistein Promotes Skeletal Muscle Regeneration by Regulating miR-221/222.
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DOI:
10.3390/ijms232113482
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发表时间:
2022-11-03
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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--
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染料木素(Genistein,Gen)是一种植物雌激素,已被报道可调节骨骼肌内分泌因子的表达和肌肉纤维类型的转换,但对其在骨骼肌再生中的作用知之甚少。作为一类广泛参与骨骼肌发育的表观遗传调节因子,microRNAs(MiRNAs)具有治疗骨骼肌损伤的潜力。在本研究中,我们发现miR-221和miR-222及其靶基因MyoG和Tnnc1是骨骼肌再生过程中的关键调控基因,并且两者都受Gen的调控。然后用C2C12成肌细胞和C2C12肌管模拟骨骼肌再生过程中肌肉卫星细胞的增殖和分化。结果表明,GEN通过抑制miR-221/222的表达,抑制卫星细胞的增殖,促进卫星细胞的分化。随后的体外和体内实验表明,Gen主要通过调节miR-221/222的表达促进中晚期卫星细胞的分化,从而促进骨骼肌再生。这些结果表明miR-221/222及其天然调节基因Gen在骨骼肌再生中具有潜在的应用前景。
Genistein (GEN), a phytoestrogen, has been reported to regulate skeletal muscle endocrine factor expression and muscle fiber type switching, but its role in skeletal muscle regeneration is poorly understood. As a class of epigenetic regulators widely involved in skeletal muscle development, microRNAs (miRNAs) have the potential to treat skeletal muscle injury. In this study, we identified miR-221 and miR-222 and their target genes MyoG and Tnnc1 as key regulators during skeletal muscle regeneration, and both were regulated by GEN. C2C12 myoblasts and C2C12 myotubes were then used to simulate the proliferation and differentiation of muscle satellite cells during skeletal muscle regeneration. The results showed that GEN could inhibit the proliferation of satellite cells and promote the differentiation of satellite cells by inhibiting the expression of miR-221/222. Subsequent in vitro and in vivo experiments showed that GEN improved skeletal muscle regeneration mainly by promoting satellite cell differentiation in the middle and late stages, by regulating miR-221/222 expression. These results suggest that miR-221/222 and their natural regulator GEN have potential applications in skeletal muscle regeneration.
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