Myostatin-1 Inhibits Cell Proliferation by Inhibiting the mTOR Signal Pathway and MRFs, and Activating the Ubiquitin-Proteasomal System in Skeletal Muscle Cells of Japanese Flounder Paralichthys olivaceus

Cells

Jiahuan Liu¹  Mingzhu Pan¹  Mengxi Yang¹  Yanlin Guo¹  Dong Huang¹  Kangsen Mai¹  Wenbing Zhang¹ 

[1] The Key Laboratory of Aquaculture Nutrition and Feeds (Ministry of Agriculture and Rural Affairs), the Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao 266003, China;

关键词: myostatin;    muscle cell;    mTOR;    Forkhead box O1;    ubiquitin-proteasomal system;   

DOI  :  10.3390/cells9112376

来源: DOAJ

【 摘 要 】

Myostatin (MSTN) is a negative regulator of skeletal muscle growth and development. The mechanisms of fish MSTN involved in muscle growth are not fully understood. In the present study, knockdown and overexpression of mstn-1 was performed in cultured Japanese flounder muscle cells to investigate the molecular function and the underlying mechanism of fish MSTN-1. Results showed that mstn-1 knockdown significantly induced cell proliferation and the mRNA expression of myogenic regulatory factors (MRFs), while overexpression of mstn-1 led to a significant decrease of cell proliferation and a suppression of the MRFs mRNA expression. The overexpression of mstn-1 also significantly increased the mRNA expression of ubiquitin–proteasomal pathway of proteolysis genes including muscle RING-finger protein 1 (murf-1) by 204.1% (p = 0.024) and muscle atrophy F-box protein (mafbx) by 165.7% (p = 0.011). However, mystn-1 overexpression inhibited the activation of mTOR signal pathway and the AKT/FoxO1 pathway through decreasing phosphorylation of AKT at Ser 473 by 56.0% (p = 0.001). Meanwhile, mystn-1 overexpression increased the dephosphorylation and nuclear localization of FoxO1 by 394.9% (p = 0.005). These results demonstrate that mstn-1 in Japanese flounder has the effects of inhibiting cell proliferation and growth, and the mTOR and AKT/FoxO1 pathways participated in these biological effects.

【 授权许可】

Unknown