Acetoacetate promotes muscle cell proliferation via the miR-133b/SRF axis through the Mek-Erk-MEF2 pathway  

作　　者：Ran Zhong Renling Miaot Jiao Meng Rimao Wu Yong Zhang Dahai Zhu 

机构地区：[1]The State Key Laboratory of Medical Molecular Biology,Chinese Academy of Medical Sciences and School of Basic Medicine,Institute of Basic Medical Sciences,Peking Union Medical College,Beijing 100005,China [2]Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory),Guangzhou 510320,China

出　　处：《Acta Biochimica et Biophysica Sinica》2021年第8期1009-1016,共8页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Natural Science Foundation of Beijing(No.7192125);the National Natural Science Foundation of China(Nos.31971080 and 91949106);the CAMS Initiative for Innovative Medicine(Nos.2016-I2M-2-006 and 2019-I2M-1-004).

摘　　要：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.

关 键 词：ACETOACETATE miR-133b MEF2 SRF muscle cells 

分 类 号：Q28[生物学—细胞生物学]