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

Abstract

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.

Fermented Yak-Kong using Bifidobacterium animalis derived from Korean infant intestine effectively relieves muscle atrophy in an aging mouse model

“…Furthermore, it is well known that isoflavones play a positive role in skeletal muscle growth and regeneration, in addition to their antioxidant and anti-inflammation effects. 16–18,45,51–54 Although our previous study used alcohol extract, it was observed through metabolomics analysis that the fermented soybean extract had a higher level of isoflavone metabolites than the unfermented one. 17 In this study, since FYK was used without an additional extraction process, it is thought that it contributed to the alleviation of muscle atrophy due to the large amount of physiologically active ingredients it contains, including metabolites previously found in the fermented soybean extract, as well as water-soluble amino acids that are beneficial for physiological activities.…”

Accounting Gut Microbiota as the Mediator of Beneficial Effects of Dietary (Poly)phenols on Skeletal Muscle in Aging

“…Interestingly, in skeletal muscle cells, genistein downregulates the expression of the micro-RNA miR-222, which is characteristically increased in muscle atrophy [ 143 ]. This mechanism can lead to muscle regeneration and regulation of muscle fiber type [ 144 , 145 ]. Finally, the isoflavone derived from licorice, glabridin, is able to reduce protein degradation and promote glucose uptake in skeletal muscle cells [ 146 , 147 ].…”