Reference - Detail
| RRC ID | 73517 |
|---|---|
| Author | Araki H, Hino S, Anan K, Kuribayashi K, Etoh K, Seko D, Takase R, Kohrogi K, Hino Y, Ono Y, Araki E, Nakao M. |
| Title | LSD1 defines the fiber type-selective responsiveness to environmental stress in skeletal muscle. |
| Journal | 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. |
| Volume | 12 |
| Published | 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 13 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | C2C12(RCB0987) |
| DNA material | pENTR4-H1 (RDB04395) CS-RfA-EVBsd (RDB06090) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (REB04394) |