目的:最近通过遗传分析发现,斯ninocalcin-2(STC2)与人类肌肉质量变异性有关。生物化学,STC2抑制金属蛋白酶PAPP-A的蛋白水解活性,通过上调胰岛素样生长因子(IGF)轴来促进肌肉生长。目的是检查STC2是否影响骨骼肌质量,并评估IGF轴如何介导功能超负荷引起的肌肉肥大。
方法:我们比较了Stc2-/-(n=21)和野生型(n=15)小鼠的肌肉质量和肌纤维形态。然后我们定量IGF1,IGF2,IGF结合蛋白-4和-5(IGFBP-4,IGFBP-5),在经受4周单侧超负荷的野生型小鼠的s肌中的PAPP-A和STC2(n=14)。
结果:与野生型小鼠相比,Stc2-/-小鼠显示出多达10%的肌肉质量。这种增加是由肌纤维的更大横截面积介导的。过载增加plant质量和IGF轴的组成部分,包括IGF1的数量(按2.41倍计算,p=0.0117),IGF2(1.70倍,p=0.0461),IGFBP-4(1.48倍,p=0.0268),PAPP-A(1.30倍,p=0.0154)和STC2(1.28倍,p=0.019)。
结论:这里我们提供证据证明STC2是肌肉生长上调的抑制剂,以及IGF轴的其他成分,在超负荷诱导的肌肉肥大期间。
Stanniocalcin-2 (STC2) has recently been implicated in human muscle mass variability by genetic analysis. Biochemically, STC2 inhibits the proteolytic activity of the metalloproteinase PAPP-A, which promotes muscle growth by upregulating the insulin-like growth factor (
IGF) axis. The aim was to examine if STC2 affects skeletal muscle mass and to assess how the
IGF axis mediates muscle hypertrophy induced by functional overload.
We compared muscle mass and muscle fiber morphology between Stc2-/- (n = 21) and wild-type (n = 15) mice. We then quantified IGF1, IGF2,
IGF binding proteins -4 and -5 (IGFBP-4, IGFBP-5), PAPP-A and STC2 in plantaris muscles of wild-type mice subjected to 4-week unilateral overload (n = 14).
Stc2-/- mice showed up to 10% larger muscle mass compared with wild-type mice. This increase was mediated by greater cross-sectional area of muscle fibers. Overload increased plantaris mass and components of the
IGF axis, including quantities of IGF1 (by 2.41-fold, p = 0.0117), IGF2 (1.70-fold, p = 0.0461), IGFBP-4 (1.48-fold, p = 0.0268), PAPP-A (1.30-fold, p = 0.0154) and STC2 (1.28-fold, p = 0.019).
Here we provide evidence that STC2 is an inhibitor of muscle growth upregulated, along with other components of the
IGF axis, during overload-induced muscle hypertrophy.