School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
Centre for Heart Lung Innovation, University of British Columbia, St. Paul's Hospital, Vancouver, Canada.
Physiol Rep. 2023 Aug;11(15):e15793. doi: 10.14814/phy2.15793.
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.
最近的遗传分析表明，钙结合蛋白 2（STC2）与人的肌肉质量变化有关。从生化角度看，STC2 可抑制蛋白水解酶 PAPP-A 的活性，通过上调胰岛素样生长因子（IGF）轴来促进肌肉生长。本研究旨在探讨 STC2 是否会影响骨骼肌质量，并评估 IGF 轴如何介导功能超负荷诱导的肌肉肥大。
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，我们对 4 周单侧超负荷（n=14）后野生型小鼠的比目鱼肌中的 IGF1、IGF2、IGF 结合蛋白-4 和-5（IGFBP-4、IGFBP-5）、PAPP-A 和 STC2 进行了定量分析。
与野生型小鼠相比，Stc2 小鼠的肌肉质量增加了 10%。这种增加是由肌纤维横截面积的增加介导的。超负荷增加了比目鱼肌的质量和 IGF 轴的各个组成部分，包括 IGF1 的含量（增加 2.41 倍，p=0.0117）、IGF2（增加 1.70 倍，p=0.0461）、IGFBP-4（增加 1.48 倍，p=0.0268）、PAPP-A（增加 1.30 倍，p=0.0154）和 STC2（增加 1.28 倍，p=0.019）。
本研究提供了证据表明，STC2 是 IGF 轴的一个抑制因子，在超负荷诱导的肌肉肥大过程中与其他 IGF 轴成分一起被上调。
