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 .

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 was performed in cultured Japanese flounder muscle cells to investigate the molecular function and the underlying mechanism of fish MSTN-1. Results showed that knockdown significantly induced cell proliferation and the mRNA expression of myogenic regulatory factors (MRFs), while overexpression of led to a significant decrease of cell proliferation and a suppression of the MRFs mRNA expression. The overexpression of also significantly increased the mRNA expression of ubiquitin-proteasomal pathway of proteolysis genes including muscle RING-finger protein 1 () by 204.1% ( = 0.024) and muscle atrophy F-box protein () by 165.7% ( = 0.011). However, overexpression inhibited the activation of mTOR signal pathway and the AKT/FoxO1 pathway through decreasing phosphorylation of AKT at Ser 473 by 56.0% ( = 0.001). Meanwhile, overexpression increased the dephosphorylation and nuclear localization of FoxO1 by 394.9% ( = 0.005). These results demonstrate that in Japanese flounder has the effects of inhibiting cell proliferation and growth, and the mTOR and AKT/FoxO1 pathways participated in these biological effects.