Research Divisions-Muscle Biology and Growth, Leibniz Institute for Farm Animal Biology, Wilhelm-Stahl-Allee 2, Dummerstorf, Germany.
Am J Physiol Endocrinol Metab. 2010 Aug;299(2):E287-98. doi: 10.1152/ajpendo.00492.2009. Epub 2010 May 25.
To elucidate the functional role of insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) for in vivo skeletal muscle growth and function, skeletal muscle cellularity and metabolism, expression of signal molecules, and body growth and composition were studied in a transgenic mouse model overexpressing IGFBP-2. Postnatal growth rate of transgenic mice was reduced from day 21 of age by 6-8% compared with nontransgenic controls. At 10 wk of age body lean protein and moisture percentages were lower, whereas fat percentage was higher in IGFBP-2 transgenic mice. Muscle weights were reduced (-13% on day 30 of age, -14% on day 72), which resulted from slower growth of myofibers in size but not from decreases in myofiber number. The reduction in muscle mass was associated with lower total DNA, RNA, and protein contents as well as greater DNA/RNA and protein/RNA ratios. The percentage of proliferating (Ki-67-positive) nuclei within myofibers was reduced (3.4 vs. 5.8%) in 30-day-old transgenic mice. These changes were accompanied by slight reductions in specific p44/42 MAPK activity (-18% on day 72) and, surprisingly, by increased levels of phosphorylated Akt (Ser(473)) (+25% on day 30, +66% on day 72). The proportion of white glycolytic fibers (55.9 vs. 53.5%) and the activity of lactate dehydrogenase (+8%) were elevated in 72-day-old transgenic mice. Most of the differences observed between transgenic and nontransgenic mice were more pronounced in males. The results suggest that IGFBP-2 significantly inhibits postnatal skeletal myofiber growth by decreasing myogenic proliferation and protein accretion and enhances glycolytic muscle metabolism.
为了阐明胰岛素样生长因子结合蛋白-2（IGFBP-2）在体内骨骼肌生长和功能中的功能作用，我们在过表达 IGFBP-2 的转基因小鼠模型中研究了骨骼肌细胞活力和代谢、信号分子的表达以及身体生长和组成。与非转基因对照相比，转基因小鼠从第 21 天开始的出生后生长速度降低了 6-8%。在 10 周龄时，IGFBP-2 转基因小鼠的体瘦肉蛋白和水分百分比较低，而脂肪百分比较高。肌肉重量降低（30 日龄时降低 13%，72 日龄时降低 14%），这是由于肌纤维大小的生长较慢，但肌纤维数量没有减少。肌肉质量的减少与总 DNA、RNA 和蛋白质含量降低以及 DNA/RNA 和蛋白质/RNA 比值增加有关。肌纤维内增殖（Ki-67 阳性）核的百分比降低（30 日龄时为 3.4%，而非转基因小鼠为 5.8%）。这些变化伴随着特定的 p44/42 MAPK 活性轻微降低（72 日龄时降低 18%），以及令人惊讶的 Akt（Ser(473)）磷酸化水平升高（30 日龄时升高 25%，72 日龄时升高 66%）。72 日龄转基因小鼠的白色糖酵解纤维（55.9%对 53.5%）比例和乳酸脱氢酶活性（+8%）升高。与非转基因小鼠相比，转基因小鼠的大多数差异在雄性中更为明显。结果表明，IGFBP-2 通过降低成肌细胞增殖和蛋白质积累，显著抑制出生后骨骼肌肌纤维的生长，并增强糖酵解肌肉代谢。
