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VDR regulates simulated microgravity-induced atrophy in C2C12 myotubes
Ryo Yuzawa1, Hiroyuki Koike1, Ichiro Manabe2
1Department of Biochemistry & Molecular Biology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
Scientific Reports
|January 27, 2022
Summary
Vitamin D receptor (VDR) plays a role in muscle atrophy. VDR deficiency protected against simulated microgravity-induced muscle wasting by regulating atrophy-related genes.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Muscle wasting, or atrophy, is a significant health issue linked to poor quality of life and increased mortality.
- Conditions like disuse, malnutrition, and microgravity cause muscle atrophy by increasing protein degradation over synthesis.
- While Vitamin D receptor (VDR) is known for calcium and phosphate regulation, emerging evidence highlights its role in skeletal muscle homeostasis and its upregulation during atrophy and injury.
Purpose of the Study:
- To investigate the role of Vitamin D receptor (VDR) in simulated microgravity-induced muscle atrophy in vitro.
- To determine if VDR mediates the repression of enhancers and regulates gene expression during microgravity exposure.
Main Methods:
- Utilized C2C12 myotubes exposed to simulated microgravity using 3D-clinorotation for 8 hours.
- Analyzed VDR-binding motifs, chromatin accessibility, and enhancer activity in response to simulated microgravity.
- Examined VDR expression, nuclear translocation, and the effects of VDR deficiency on muscle atrophy and FBXO32 induction.
Main Results:
- Simulated microgravity led to VDR-binding motifs associating with closed chromatin regions and inactivated enhancers, suggesting VDR mediates enhancer repression.
- VDR expression was induced, and it translocated into the nuclei of myotubes under simulated microgravity.
- C2C12 myotubes lacking VDR exhibited resistance to simulated microgravity-induced atrophy and showed reduced induction of the atrophy-associated gene FBXO32.
Conclusions:
- Vitamin D receptor (VDR) is implicated in the regulation of muscle atrophy induced by simulated microgravity.
- VDR appears to control the expression of atrophy-related genes, including FBXO32, contributing to the muscle wasting process.
- These findings suggest VDR is a key factor in skeletal muscle's response to microgravity, offering potential therapeutic targets for muscle atrophy.
