Department of Immunology, Laboratory of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju, 380-701, Seoul, South Korea.
Dandi Bioscience Inc, 6th Floor of Real Company, 66, Acha San-ro, Seongdong-gu, Seoul, South Korea.
Biochem Biophys Res Commun. 2021 Mar 5;543:1-7. doi: 10.1016/j.bbrc.2021.01.030. Epub 2021 Feb 12.
Muscle wasting caused by catabolic reactions in skeletal muscle is commonly observed in patients with sepsis. Myostatin, a negative regulator of muscle mass, has been reported to be upregulated in diseases associated with muscle atrophy. However, the behavior of myostatin during sepsis is not well understood. Herein, we sought to investigate the expression and regulation of myostatin in skeletal muscle in mice inoculated with gram-negative bacteria. Interestingly, the protein level of myostatin was found to increase in the muscle of septic mice simultaneously with an increase in the levels of follistatin, NF-κΒ, myogenin, MyoD, p- FOXO3a, and p-Smad2. Furthermore, the inhibition of myostatin by YK11 repressed the levels of pro-inflammatory cytokines and organ damage markers in the bloodstream and in the major organs of mice, which originally increased in sepsis; thus, myostatin inhibition by YK11 decreased the mortality rate due to sepsis. The results of this study suggest that YK11 may help revert muscle wasting during sepsis and subdue the inflammatory environment, thereby highlighting its potential as a preventive agent for sepsis-related muscle wasting.
在脓毒症患者中，常观察到骨骼肌肉中分解代谢反应引起的肌肉减少。肌生成抑制素是肌肉质量的负调节剂，已报道其在与肌肉萎缩相关的疾病中上调。然而，肌生成抑制素在脓毒症中的行为尚不清楚。在此，我们试图研究革兰氏阴性菌接种的小鼠骨骼肌中肌生成抑制素的表达和调节。有趣的是，同时发现脓毒症小鼠的肌肉中肌生成抑制素蛋白水平增加，而 follistatin、NF-κB、myogenin、MyoD、p-FOXO3a 和 p-Smad2 的水平也增加。此外，肌生成抑制素的抑制物 YK11 抑制了脓毒症小鼠血液和主要器官中促炎细胞因子和器官损伤标志物的水平，这些标志物在脓毒症中最初增加；因此，YK11 抑制肌生成抑制素降低了脓毒症导致的死亡率。本研究结果表明，YK11 可能有助于逆转脓毒症期间的肌肉减少并抑制炎症环境，从而凸显其作为预防脓毒症相关肌肉减少的潜在用途。
