Abstract
Hypertrophic stimuli, such as mechanical stress and overloading, induce stress response, which is mediated by heat shock transcription factor 1 (HSF1), and up-regulate heat shock proteins (HSPs) in mammalian skeletal muscles. Therefore, HSF1-associated stress response may play a key role in loading-associated skeletal muscle hypertrophy. The purpose of this study was to investigate the effects of HSF1-deficiency on skeletal muscle hypertrophy caused by overloading. Functional overloading on the left soleus was performed by cutting the distal tendons of gastrocnemius and plantaris muscles for 4 weeks. The right muscle served as the control. Soleus muscles from both hindlimbs were dissected 2 and 4 weeks after the operation. Hypertrophy of soleus muscle in HSF1-null mice was partially inhibited, compared with that in wild-type (C57BL/6J) mice. Absence of HSF1 partially attenuated the increase of muscle wet weight and fiber cross-sectional area of overloaded soleus muscle. Population of Pax7-positive muscle satellite cells in HSF1-null mice was significantly less than that in wild-type mice following 2 weeks of overloading (p<0.05). Significant up-regulations of interleukin (IL)-1β and tumor necrosis factor mRNAs were observed in HSF1-null, but not in wild-type, mice following 2 weeks of overloading. Overloading-related increases of IL-6 and AFT3 mRNA expressions seen after 2 weeks of overloading tended to decrease after 4 weeks in both types of mice. In HSF1-null mice, however, the significant overloading-related increase in the expression of IL-6, not ATF3, mRNA was noted even at 4th week. Inhibition of muscle hypertrophy might be attributed to the greater and prolonged enhancement of IL-6 expression. HSF1 and/or HSF1-mediated stress response may, in part, play a key role in loading-induced skeletal muscle hypertrophy.
Highlights
Mechanical loading is one of the important factors in the regulation of skeletal muscle size
There was no significant difference in the absolute muscle wet weight and proteins content of the contralateral control soleus muscle between wild-type and Heat shock transcription factors (HSFs)-null mice
Present study showed that absence of heat shock transcription factor 1 (HSF1) partially inhibited the overloading-associated increments of muscle wet weight, protein content, and fiber cross-sectional area (CSA) of mouse soleus muscle
Summary
Mechanical loading is one of the important factors in the regulation of skeletal muscle size. Skeletal muscle is highly plastic and adapts to physical demand. Increase in the mechanical load on skeletal muscle causes hypertrophy, whereas unloading induces atrophy. It has been generally accepted that increased loading activates muscle satellite cells, which are skeletal muscle-specific stem cells, and stimulates muscle protein synthesis. Hypertrophied muscle fibers, caused by mechanical loading, have a larger diameter, greater protein content, and increased number of myonuclei compared with sedentary control fibers. Loading-dependent muscle hypertrophy is attributed to both the activation of muscle satellite cells and the stimulation of protein synthesis [1,2], the mechanisms responsible for these systems are not fully elucidated
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