Changes in FOXO and proinflammatory cytokines in the late stage of immobilized fast and slow muscle atrophy.

The present study aimed to examine the changes in the expression of Forkhead box protein O (FOXO) and proinflammatory cytokines in both slow-twitch soleus and fast-twitch plantaris muscles following cast immobilization. Male C57BL/6 mice were subjected to cast immobilization for 7 and 21 days. Cast immobilization increased FOXO3a mRNA and total protein expression in both the soleus and plantaris muscles. Although FOXO3a phosphorylation tended to increase in response to cast immobilization in both muscles, a significant increase was evident after 21 days of immobilization only in the soleus muscle. The degree of the response of FOXO3a was very different between the soleus and plantaris muscles; however, the kinetics of FOXO3a in both muscles were similar. Thus, the regulation of muscle atrophy by FOXO might act via a common mechanism in both slow-twitch soleus and fast-twitch plantaris muscles. Gene expression of proinflammatory cytokines tended to increase in response to cast immobilization, and a significant increase was evident after 21 days of immobilization in the soleus muscle. However, in the plantaris muscle, proinflammatory cytokine gene expression remained unchanged throughout the immobilization period; nevertheless, immobilization induced greater reduction in muscle fiber cross-sectional area in the plantaris than in the soleus muscle. Thus, these observations indicate that regulation of muscle atrophy by proinflammatory cytokines might contribute to muscle fiber type-specific mechanisms.