VDR regulates simulated microgravity-induced atrophy in C2C12 myotubes.
VDR regulates simulated microgravity-induced atrophy in C2C12 myotubes.
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DOI：
10.1038/s41598-022-05354-0
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发表时间：
2022-01-26
影响因子：
4.6
通讯作者：
Oishi Y
中科院分区：
文献类型：
--
作者：
Yuzawa R;Koike H;Manabe I;Oishi Y
肌肉萎缩是导致生活质量下降以及死亡和各种疾病风险增加的一个主要问题。肌肉萎缩是由蛋白质降解超过其合成的多种情况引起的，包括废用、营养不良和微重力。众所周知，维生素 D 受体 (VDR) 可以调节钙和磷酸盐代谢以维持骨骼，但最近的研究表明，VDR 在骨骼肌发育和体内平衡中也发挥着作用。此外，其表达在肌肉萎缩以及肌肉损伤后上调。在这里，我们证明 VDR 在体外调节 C2C12 肌管模拟微重力诱导的萎缩。使用 3D 旋转模拟微重力 8 小时后，VDR 结合基序与模拟微重力封闭的染色质区域和由此失活的增强子区域相关，这表明 VDR 介导增强子的抑制。此外，响应模拟微重力，VDR 被诱导并转移到细胞核中。 VDR 缺陷的 C2C12 肌管表现出对模拟微重力诱导的萎缩的抵抗力，并减少了 FBXO32（一种萎缩相关的泛素连接酶）的诱导。这些结果表明，VDR 至少部分通过控制萎缩相关基因的表达来调节模拟微重力诱导的萎缩。
Muscle wasting is a major problem leading to reduced quality of life and higher risks of mortality and various diseases. Muscle atrophy is caused by multiple conditions in which protein degradation exceeds its synthesis, including disuse, malnutrition, and microgravity. While Vitamin D receptor (VDR) is well known to regulate calcium and phosphate metabolism to maintain bone, recent studies have shown that VDR also plays roles in skeletal muscle development and homeostasis. Moreover, its expression is upregulated in muscle undergoing atrophy as well as after muscle injury. Here we show that VDR regulates simulated microgravity-induced atrophy in C2C12 myotubes in vitro. After 8 h of microgravity simulated using 3D-clinorotation, the VDR-binding motif was associated with chromatin regions closed by the simulated microgravity and enhancer regions inactivated by it, which suggests VDR mediates repression of enhancers. In addition, VDR was induced and translocated into the nuclei in response to simulated microgravity. VDR-deficient C2C12 myotubes showed resistance to simulated microgravity-induced atrophy and reduced induction of FBXO32, an atrophy-associated ubiquitin ligase. These results demonstrate that VDR contributes to the regulation of simulated microgravity-induced atrophy at least in part by controlling expression of atrophy-related genes.
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DOI：
10.1113/jp280652
发表时间：
2021-03
期刊：
The Journal of physiology
影响因子：
--
作者：
Bass JJ;Kazi AA;Deane CS;Nakhuda A;Ashcroft SP;Brook MS;Wilkinson DJ;Phillips BE;Philp A;Tarum J;Kadi F;Andersen D;Garcia AM;Smith K;Gallagher IJ;Szewczyk NJ;Cleasby ME;Atherton PJ
通讯作者：
Atherton PJ
影响因子：
4.8
作者：
Garcia, Leah A.;King, Keisha K.;Artaza, Jorge N.
通讯作者：
Artaza, Jorge N.
影响因子：
4.2
作者：
Girgis, Christian M.;Cha, Kuan Minn;Gunton, Jenny E.
通讯作者：
Gunton, Jenny E.
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
5.1
作者：
Furukawa T;Tanimoto K;Fukazawa T;Imura T;Kawahara Y;Yuge L
通讯作者：
Yuge L