PDF(Pubmed)
Abstract：
An intriguing effect of short-term caloric restriction (CR) is the expansion of certain stem cell populations, including muscle stem cells (satellite cells), which facilitate an accelerated regenerative program after injury. Here, we utilized the MetRSL274G (MetRS) transgenic mouse to identify liver-secreted plasminogen as a candidate for regulating satellite cell expansion during short-term CR. Knockdown of circulating plasminogen prevents satellite cell expansion during short-term CR. Furthermore, loss of the plasminogen receptor KT (Plg-RKT) is also sufficient to prevent CR-related satellite cell expansion, consistent with direct signaling of plasminogen through the plasminogen receptor Plg-RKT/ERK kinase to promote proliferation of satellite cells. Importantly, we are able to replicate many of these findings in human participants from the CALERIE trial. Our results demonstrate that CR enhances liver protein secretion of plasminogen, which signals directly to the muscle satellite cell through Plg-RKT to promote proliferation and subsequent muscle resilience during CR.
摘要：
短期热量限制（CR）的一个有趣的效果是某些干细胞群体的扩增，包括肌肉干细胞（卫星细胞），这有助于受伤后加速再生程序。这里,我们利用MetRSL274G(MetRS)转基因小鼠鉴定肝脏分泌型纤溶酶原作为短期CR期间调节卫星细胞扩增的候选物.循环纤溶酶原的敲除可防止短期CR期间的卫星细胞扩增。此外，纤溶酶原受体KT（Plg-RKT）的丢失也足以阻止CR相关的卫星细胞扩增，与纤溶酶原通过纤溶酶原受体Plg-RKT/ERK激酶促进卫星细胞增殖的直接信号传导一致。重要的是,我们能够在CALERIE试验的人类参与者中复制许多这些发现.我们的结果表明，CR增强纤溶酶原的肝脏蛋白分泌，通过Plg-RKT直接向肌肉卫星细胞发出信号，以促进CR期间的增殖和随后的肌肉弹性。
