title: Heat shock transcription factor 1-deficiency attenuates overloading-associated hypertrophy of mouse soleus muscle.
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.
authors.affiliation: Department of Orthopaedic Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Koya
authors.forename: Sono
authors.initials: S
authors.lastname: Nishizawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ohno
authors.forename: Ayumi
authors.initials: A
authors.lastname: Goto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ikuta
authors.forename: Miho
authors.initials: M
authors.lastname: Suzuki
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Ohira
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Egawa
authors.forename: Akira
authors.initials: A
authors.lastname: Nakai
authors.forename: Takao
authors.initials: T
authors.lastname: Sugiura
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ohira
authors.forename: Toshitada
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Moroe
authors.initials: M
authors.lastname: Beppu
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Goto
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D000076249:Heat Shock Transcription Factors; D006984:Hypertrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D015850:Interleukin-6; D009124:Muscle Proteins; D012333:RNA, Messenger; D014157:Transcription Factors