Department of Cell Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Cell. 2012 Dec 7;151(6):1319-31. doi: 10.1016/j.cell.2012.10.050.
PGC-1α is a transcriptional coactivator induced by exercise that gives muscle many of the best known adaptations to endurance-type exercise but has no effects on muscle strength or hypertrophy. We have identified a form of PGC-1α (PGC-1α4) that results from alternative promoter usage and splicing of the primary transcript. PGC-1α4 is highly expressed in exercised muscle but does not regulate most known PGC-1α targets such as the mitochondrial OXPHOS genes. Rather, it specifically induces IGF1 and represses myostatin, and expression of PGC-1α4 in vitro and in vivo induces robust skeletal muscle hypertrophy. Importantly, mice with skeletal muscle-specific transgenic expression of PGC-1α4 show increased muscle mass and strength and dramatic resistance to the muscle wasting of cancer cachexia. Expression of PGC-1α4 is preferentially induced in mouse and human muscle during resistance exercise. These studies identify a PGC-1α protein that regulates and coordinates factors involved in skeletal muscle hypertrophy.
PGC-1α 是一种由运动诱导的转录共激活因子，它使肌肉对耐力型运动产生了许多最著名的适应性，但对肌肉力量或肥大没有影响。我们已经确定了一种 PGC-1α 的形式（PGC-1α4），它是由不同的启动子使用和主要转录物的剪接产生的。PGC-1α4 在运动后的肌肉中高度表达，但不调节大多数已知的 PGC-1α 靶标，如线粒体 OXPHOS 基因。相反，它特异性地诱导 IGF1 并抑制肌肉生长抑制素，PGC-1α4 在体外和体内的表达诱导出强健的骨骼肌肥大。重要的是，具有骨骼肌特异性过表达 PGC-1α4 的小鼠表现出肌肉质量和力量的增加，以及对癌症恶病质导致的肌肉消耗的显著抵抗力。在抵抗运动过程中，PGC-1α4 在小鼠和人类肌肉中的表达被优先诱导。这些研究确定了一种 PGC-1α 蛋白，它调节和协调参与骨骼肌肥大的因素。
