当前位置: X-MOL 学术Proc. Natl. Acad. Sci. U.S.A. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight.
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2020-09-22 , DOI: 10.1073/pnas.2014716117
Se-Jin Lee 1, 2 , Adam Lehar 3 , Jessica U Meir 4 , Christina Koch 4 , Andrew Morgan 4 , Lara E Warren 5 , Renata Rydzik 6 , Daniel W Youngstrom 6 , Harshpreet Chandok 3 , Joshy George 3 , Joseph Gogain 7 , Michael Michaud 3 , Thomas A Stoklasek 3 , Yewei Liu 3 , Emily L Germain-Lee 8, 9
Affiliation  

Among the physiological consequences of extended spaceflight are loss of skeletal muscle and bone mass. One signaling pathway that plays an important role in maintaining muscle and bone homeostasis is that regulated by the secreted signaling proteins, myostatin (MSTN) and activin A. Here, we used both genetic and pharmacological approaches to investigate the effect of targeting MSTN/activin A signaling in mice that were sent to the International Space Station. Wild type mice lost significant muscle and bone mass during the 33 d spent in microgravity. Muscle weights of Mstn −/− mice, which are about twice those of wild type mice, were largely maintained during spaceflight. Systemic inhibition of MSTN/activin A signaling using a soluble form of the activin type IIB receptor (ACVR2B), which can bind each of these ligands, led to dramatic increases in both muscle and bone mass, with effects being comparable in ground and flight mice. Exposure to microgravity and treatment with the soluble receptor each led to alterations in numerous signaling pathways, which were reflected in changes in levels of key signaling components in the blood as well as their RNA expression levels in muscle and bone. These findings have implications for therapeutic strategies to combat the concomitant muscle and bone loss occurring in people afflicted with disuse atrophy on Earth as well as in astronauts in space, especially during prolonged missions.



中文翻译:


靶向肌生长抑制素/激活素 A 可防止太空飞行期间骨骼肌和骨质流失。



长时间太空飞行的生理后果包括骨骼肌和骨质流失。在维持肌肉和骨骼稳态中起重要作用的一种信号通路是由分泌的信号蛋白、肌肉生长抑制素(MSTN)和激活素 A 调节的。在这里,我们使用遗传和药理学方法来研究靶向 MSTN/激活素 A 的效果被送往国际空间站的老鼠身上发出的信号。野生型小鼠在微重力下度过 33 天期间,肌肉和骨量明显减少。 Mstn −/−小鼠的肌肉重量约为野生型小鼠的两倍,在太空飞行期间基本保持不变。使用可溶形式的激活素 IIB 型受体 (ACVR2B)(可以结合这些配体中的每一种)对 MSTN/激活素 A 信号传导进行系统性抑制,导致肌肉和骨量显着增加,其效果在地面和飞行小鼠中相当。暴露于微重力和使用可溶性受体进行治疗都会导致许多信号通路的改变,这反映在血液中关键信号成分水平的变化以及肌肉和骨骼中的 RNA 表达水平的变化上。这些发现对于治疗地球上患有废用性萎缩的人以及太空宇航员(尤其是在长期任务期间)伴随的肌肉和骨质流失的治疗策略具有重要意义。

更新日期:2020-09-23
down
wechat
bug