| RRC ID |
73517
|
| 著者 |
Araki H, Hino S, Anan K, Kuribayashi K, Etoh K, Seko D, Takase R, Kohrogi K, Hino Y, Ono Y, Araki E, Nakao M.
|
| タイトル |
LSD1 defines the fiber type-selective responsiveness to environmental stress in skeletal muscle.
|
| ジャーナル |
Elife
|
| Abstract |
Skeletal muscle exhibits remarkable plasticity in response to environmental cues, with stress-dependent effects on the fast-twitch and slow-twitch fibers. Although stress-induced gene expression underlies environmental adaptation, it is unclear how transcriptional and epigenetic factors regulate fiber type-specific responses in the muscle. Here, we show that flavin-dependent lysine-specific demethylase-1 (LSD1) differentially controls responses to glucocorticoid and exercise in postnatal skeletal muscle. Using skeletal muscle-specific LSD1-knockout mice and in vitro approaches, we found that LSD1 loss exacerbated glucocorticoid-induced atrophy in the fast fiber-dominant muscles, with reduced nuclear retention of Foxk1, an anti-autophagic transcription factor. Furthermore, LSD1 depletion enhanced endurance exercise-induced hypertrophy in the slow fiber-dominant muscles, by induced expression of ERRγ, a transcription factor that promotes oxidative metabolism genes. Thus, LSD1 serves as an 'epigenetic barrier' that optimizes fiber type-specific responses and muscle mass under the stress conditions. Our results uncover that LSD1 modulators provide emerging therapeutic and preventive strategies against stress-induced myopathies such as sarcopenia, cachexia, and disuse atrophy.
|
| 巻・号 |
12
|
| 公開日 |
2023-1-25
|
| DOI |
10.7554/eLife.84618
|
| PII |
84618
|
| PMID |
36695573
|
| PMC |
PMC9876571
|
| MeSH |
Animals
Glucocorticoids* / metabolism
Histone Demethylases / genetics
Histone Demethylases / metabolism
Mice
Muscle Fibers, Skeletal / metabolism
Muscle, Skeletal / metabolism
Muscular Diseases*
Transcription Factors / metabolism
|
| IF |
7.08
|
| リソース情報 |
| ヒト・動物細胞 |
C2C12(RCB0987) |
