論文 - 詳細
| RRC ID | 54005 |
|---|---|
| 著者 | Yuasa K, Okubo K, Yoda M, Otsu K, Ishii Y, Nakamura M, Itoh Y, Horiuchi K. |
| タイトル | Targeted ablation of p38α MAPK suppresses denervation-induced muscle atrophy. |
| ジャーナル | Sci Rep |
| Abstract |
The loss of skeletal muscle mass is a major cause of falls and fractures in the elderly, leading to compromised independence and a decrease in the quality of life. However, only a few therapeutic interventions leading to marginal clinical benefits in patients with this condition are currently available. Therefore, the demand to further understand the pathology of muscle atrophy and establish a treatment modality for patients with muscle atrophy is significant. p38α mitogen-activated protein kinase (p38α MAPK) is a ubiquitous signaling molecule that is implicated in various cellular functions, including cell proliferation, differentiation, and senescence. In the present study, we generated a mutant line in which p38α MAPK is specifically abrogated in muscle tissues. Compared with the control mice, these mutant mice are significantly resistant to denervation-induced muscle atrophy, suggesting that p38α MAPK positively regulates muscle atrophy. We also identified CAMK2B as a potential downstream target of p38α MAPK and found that the pharmacological inhibition of CAMK2B activity suppresses denervation-induced muscle atrophy. Altogether, our findings identify p38α MAPK as a novel regulator of muscle atrophy and suggest that the suppression of intracellular signaling mediated by p38α MAPK serves as a potential target for the treatment of muscle atrophy. |
| 巻・号 | 8(1) |
| ページ | 9037 |
| 公開日 | 2018-6-13 |
| DOI | 10.1038/s41598-018-26632-w |
| PII | 10.1038/s41598-018-26632-w |
| PMID | 29899565 |
| PMC | PMC5998077 |
| MeSH | Animals Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism* Cell Line Denervation Enzyme Inhibitors / pharmacology Humans Male Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors Mitogen-Activated Protein Kinase 14 / genetics Mitogen-Activated Protein Kinase 14 / metabolism* Molecular Targeted Therapy / methods Muscle, Skeletal / drug effects Muscle, Skeletal / enzymology* Muscle, Skeletal / pathology Muscular Atrophy / enzymology* Muscular Atrophy / pathology Muscular Atrophy / prevention & control Signal Transduction / drug effects Signal Transduction / genetics |
| IF | 3.998 |
| 引用数 | 3 |
| 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 | 1 |
| 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) |