論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 13 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | C2C12(RCB0987) |
| 遺伝子材料 | pENTR4-H1 (RDB04395) CS-RfA-EVBsd (RDB06090) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (REB04394) |