Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27701, USA.
Proteomics and Metabolomics Core Facility, Duke University School of Medicine, Durham, NC, USA.
Cell Rep. 2024 Mar 26;43(3):113881. doi: 10.1016/j.celrep.2024.113881. Epub 2024 Mar 4.
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 MetRS (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-R) is also sufficient to prevent CR-related satellite cell expansion, consistent with direct signaling of plasminogen through the plasminogen receptor Plg-R/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-R to promote proliferation and subsequent muscle resilience during CR.
短期热量限制（CR）的一个有趣作用是扩展某些干细胞群体，包括肌肉干细胞（卫星细胞），这有助于在损伤后加速再生程序。在这里，我们利用 MetRS（MetRS）转基因小鼠来鉴定肝脏分泌的纤溶酶原作为调节短期 CR 期间卫星细胞扩增的候选物。循环纤溶酶原的敲低可防止短期 CR 期间卫星细胞的扩增。此外，纤溶酶原受体 KT（Plg-R）的缺失也足以防止与 CR 相关的卫星细胞扩增，这与纤溶酶原通过纤溶酶原受体 Plg-R/ERK 激酶直接信号转导以促进卫星细胞增殖一致。重要的是，我们能够在来自 CALERIE 试验的人类参与者中复制许多这些发现。我们的研究结果表明，CR 增强了肝脏纤溶酶原的蛋白质分泌，通过 Plg-R 直接作用于肌肉卫星细胞，促进增殖，并在 CR 期间促进肌肉恢复能力。
Zotero 插件
