Six1 and Six1 cofactor expression is altered during early skeletal muscle overload in mice.
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abstract
Six1 is a transcription factor that, along with cofactors (Eya1, Eya3, and Dach2), regulates skeletal muscle fiber-type and development. SIX1 (human) gene expression decreases after overload, but the time course of Six1 expression, if protein is affected, and if the response differs between muscles with differing phenotypes, is not known. Our purpose was to examine Six1 gene and protein expression and co-factor gene expression during the initiation of muscle overload, and determine if the muscle phenotype altered this response. The plantaris and soleus were functionally overloaded by synergistic ablation of the gastrocnemius, and Six1 gene and protein, and Six1 cofactor gene expression was measured. Six1 gene expression decreased at 1day of overload 489 and 4720% (p<0.01) in the plantaris and soleus. After 3days of overload, Six1 protein expression increased 7317 and 16857% in the plantaris and soleus (p<0.05). After 1day of overload, Dach2 gene expression decreased 569 and 353% in both muscles (p<0.001), while Eya1 decreased 335% only in the soleus (p<0.01). Eya3 gene expression increased 12726% (p<0.05) and 7616% (p<0.05) in the plantaris and soleus, while Dach2 gene expression decreased 714% (p<0.05) in the soleus after 3days of overload. Six1 and Six1 co-factor expression is responsive to muscle overload in both fast and slow muscles. This indicates that this molecular program may affect overload adaptation regardless of muscle phenotype.
