Heat shock transcription factor 1-deficiency attenuates overloading-associated hypertrophy of mouse soleus muscle.
Heat shock transcription factor 1-deficiency attenuates overloading-associated hypertrophy of mouse soleus muscle.
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DOI：
10.1371/journal.pone.0077788
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Goto K
中科院分区：
文献类型：
--
作者：
Koya T;Nishizawa S;Ohno Y;Goto A;Ikuta A;Suzuki M;Ohira T;Egawa T;Nakai A;Sugiura T;Ohira Y;Yoshioka T;Beppu M;Goto K
机械应激和超负荷等肥大刺激诱导由热休克转录因子1(HSF1)介导的应激反应，并上调哺乳动物骨骼肌中热休克蛋白(HSPs)的表达。因此，HSF1相关的应激反应可能在负荷性骨骼肌肥大中起关键作用。本研究旨在探讨HSF1缺乏对超负荷所致骨骼肌肥大的影响。切断腓肠肌和足底肌远端肌腱4周，造成左侧比目鱼肌功能超负荷。右侧肌肉作为对照。术后2周和4周解剖双后肢比目鱼肌。与野生型(C57BL/6J)小鼠相比，HSF1基因缺失小鼠的比目鱼肌肥大受到部分抑制。HSF1的缺失部分缓解了超负荷比目鱼肌肌湿重和纤维横截面积的增加。在超负荷2周后，HSF1基因缺失小鼠的Pax7阳性肌肉卫星细胞数量显著少于野生型小鼠(p<；0.05)。在超负荷2周后，观察到白介素1β和肿瘤坏死因子mRNAs在hsf1缺失的小鼠中显著上调，但在野生型小鼠中没有明显上调。在两种类型的小鼠中，与超负荷相关的IL-6和AFT3mRNA的表达在超负荷2周后出现上升，在4周后趋于下降。然而，在HSF1基因缺失的小鼠中，即使在第4周，也观察到了与超负荷相关的IL-6而不是ATF3基因表达的显著增加。抑制肌肉肥大可能是由于IL-6的表达增强幅度更大且持续时间更长。HSF1和/或HSF1介导的应激反应可能在负荷诱导的骨骼肌肥大中起关键作用。
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.
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