Perlecan deficiency causes muscle hypertrophy, a decrease in myostatin expression, and changes in muscle fiber composition.
Perlecan deficiency causes muscle hypertrophy, a decrease in myostatin expression, and changes in muscle fiber composition.
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基底膜蛋白缺乏会导致肌肉肥大、肌生长抑制素表达减少以及肌纤维组成发生变化。
DOI：
10.1016/j.matbio.2010.06.001
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Arikawa-Hirasawa,Eri
中科院分区：
文献类型：
--
作者：
Xu,Zhuo;Ichikawa,Naoki;Kosaki,Keisuke;Yamada,Yoshihiko;Sasaki,Takako;Sakai,LynnY;Kurosawa,Hisashi;Hattori,Nobutaka;Arikawa-Hirasawa,Eri
串珠素是骨骼肌周围基底膜的一种成分。本研究的目的是使用骨骼肌串珠素缺陷的小鼠模型（Hspg 2 −/−-Tg），在有和没有机械应力的情况下，确定串珠素在骨骼肌肥大和肌生长抑制素信号传导中的作用。我们发现，与对照（WT-Tg）小鼠相比，Hspg 2 −/−-Tg小鼠胫骨前肌（TA）中的肌球蛋白重链（MHC）IIb型纤维具有显著增加的纤维横截面积（CSA）。Hspg 2 −/−-Tg小鼠TA肌肉中的IIx型纤维数量也有所增加。肌生长抑制素及其I型受体（ALK 4）的表达在Hspg 2 −/−-Tg TA肌肉中显著降低。在来自Hspg 2 −/−-Tg肌肉的肌管培养物中，肌生长抑制素诱导的Smad活化也减少，表明肌生长抑制素的表达及其信号传导在Hspg 2 −/−-Tg肌肉中减少。为了研究机械过载或卸载对Hspg 2 −/−-Tg小鼠快肌和慢肌的影响，我们对跖肌（快）和比目鱼肌（慢）进行了肌腱切断术。与对照组小鼠相比，Hspg 2 −/−-Tg小鼠的足底肌肉上的机械过载显著增加了湿重，与对照组小鼠相比，Hspg 2 −/−-Tg小鼠的足底肌肉的卸载导致湿重减少较少。与对照组小鼠相比，Hspg 2 −/−-Tg小鼠的跖肌中肌生长抑制素表达的降低显著。相比之下，超负荷的比目鱼肌不会引起任何类型的肌肉的变化。这些结果表明串珠素对于维持快速肌肉质量和纤维组成以及调节肌生长抑制素信号传导是至关重要的。
Perlecan is a component of the basement membrane that surrounds skeletal muscle. The aim of the present study is to identify the role of perlecan in skeletal muscle hypertrophy and myostatin signaling, with and without mechanical stress, using a mouse model (Hspg2−/−-Tg) deficient in skeletal muscle perlecan. We found that myosin heavy chain (MHC) type IIb fibers in the tibialis anterior (TA) muscle of Hspg2−/−-Tg mice had a significantly increased fiber cross-sectional area (CSA) compared to control (WT-Tg) mice. Hspg2−/−-Tg mice also had an increased number of type IIx fibers in the TA muscle. Myostatin and its type I receptor (ALK4) expression was substantially decreased in the Hspg2−/−-Tg TA muscle. Myostatin-induced Smad activation was also reduced in a culture of myotubes from the Hspg2−/−-Tg muscle, suggesting that myostatin expression and its signaling were decreased in the Hspg2−/−-Tg muscle. To examine the effects of mechanical overload or unload on fast and slow muscles in Hspg2−/−-Tg mice, we performed tenotomy of the plantaris (fast) muscle and the soleus (slow) muscle. Mechanical overload on the plantaris muscle of Hspg2−/−-Tg mice significantly increased wet weights compared to those of control mice, and unloaded plantaris muscles of Hspg2−/−-Tg mice caused less decrease in wet weights compared to those of control mice. The decrease in myostatin expression was significantly profound in the overloaded plantaris muscle of Hspg2−/−-Tg mice, compared with that of control mice. In contrast, overloading the soleus muscle caused no changes in either type of muscle. These results suggest that perlecan is critical for maintaining fast muscle mass and fiber composition, and for regulating myostatin signaling.