Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 21, Pages -Publisher
MDPI
DOI: 10.3390/ijms232113482
Keywords
genistein; muscle regeneration; miR-222; miR-221
Funding
- National Natural Science Foundation of China [31902135]
- Sichuan Science and Technology Program [2021YFYZ0007, 2020YFN0147, 2021ZDZX0008, scsztd-2022-08-09]
- China Agriculture Research System of MOF and MARA
- National Center of Technology Innovation for Pigs
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The study identified miR-221 and miR-222 and their target genes MyoG and Tnnc1 as key regulators during skeletal muscle regeneration, both regulated by GEN. GEN promotes satellite cell differentiation during skeletal muscle regeneration by inhibiting the expression of miR-221/222.
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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