Acetoacetate promotes muscle cell proliferation via the miR-133b/SRF axis through the Mek-Erk-MEF2 pathway.
Acta Biochim Biophys Sin (Shanghai)
; 53(8): 1009-1016, 2021 Jul 28.
Article
in En
| MEDLINE
| ID: mdl-34184741
ABSTRACT
Acetoacetate (AA) is an important ketone body that is used as an oxidative fuel to supply energy for the cellular activities of various tissues, including the brain and skeletal muscle. We recently revealed a new signaling role for AA by showing that it promotes muscle cell proliferation in vitro, enhances muscle regeneration in vivo, and ameliorates the dystrophic muscle phenotype of Mdx mice. In this study, we provide new molecular insight into this function of AA. We show that AA promotes C2C12 cell proliferation by transcriptionally upregulating the expression of muscle-specific miR-133b, which in turn stimulates muscle cell proliferation by targeting serum response factor. Furthermore, we show that the AA-induced upregulation of miR-133b is transcriptionally mediated by MEF2 via the Mek-Erk1/2 signaling pathway. Mechanistically, our findings provide further convincing evidence that AA acts as signaling metabolite to actively regulate various cellular activities in mammalian cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
MAP Kinase Signaling System
/
Serum Response Factor
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Myoblasts
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MicroRNAs
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Cell Proliferation
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Acetoacetates
Limits:
Animals
Language:
En
Journal:
Acta Biochim Biophys Sin (Shanghai)
Journal subject:
BIOFISICA
/
BIOQUIMICA
Year:
2021
Document type:
Article
Affiliation country:
China