論文 - 詳細
| RRC ID | 49637 |
|---|---|
| 著者 | Hatazawa Y, Ono Y, Hirose Y, Kanai S, Fujii NL, Machida S, Nishino I, Shimizu T, Okano M, Kamei Y, Ogawa Y. |
| タイトル | Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration. |
| ジャーナル | FASEB J |
| Abstract |
DNA methylation is an epigenetic mechanism regulating gene expression. In this study, we observed that DNA methyltransferase 3a (Dnmt3a) expression is decreased after muscle atrophy. We made skeletal muscle-specific Dnmt3a-knockout (Dnmt3a-KO) mice. The regeneration capacity after muscle injury was markedly decreased in Dnmt3a-KO mice. Diminished mRNA and protein expression of Dnmt3a were observed in skeletal muscles as well as in satellite cells, which are important for muscle regeneration, in Dnmt3a-KO mice. Dnmt3a-KO satellite cell showed smaller in size (length/area), suggesting suppressed myotube differentiation. Microarray analysis of satellite cells showed that expression of growth differentiation factor 5 (Gdf5) mRNA was markedly increased in Dnmt3a-KO mice. The DNA methylation level of the Gdf5 promoter was markedly decreased in Dnmt3a-KO satellite cells. In addition, DNA methylation inhibitor azacytidine treatment increased Gdf5 expression in wild-type satellite cells, suggesting Gdf5 expression is regulated by DNA methylation. Also, we observed increased inhibitor of differentiation (a target of Gdf5) mRNA expression in Dnmt3a-KO satellite cells. Thus, Dnmt3a appears to regulate satellite cell differentiation via DNA methylation. This mechanism may play a role in the decreased regeneration capacity during atrophy such as in aged sarcopenia.-Hatazawa, Y., Ono, Y., Hirose, Y., Kanai, S., Fujii, N. L., Machida, S., Nishino, I., Shimizu, T., Okano, M., Kamei, Y., Ogawa, Y. Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration. |
| 巻・号 | 32(3) |
| ページ | 1452-1467 |
| 公開日 | 2018-3-1 |
| DOI | 10.1096/fj.201700573R |
| PII | fj.201700573R |
| PMID | 29146735 |
| MeSH | Animals Cell Differentiation* DNA (Cytosine-5-)-Methyltransferases / genetics DNA (Cytosine-5-)-Methyltransferases / metabolism* DNA Methyltransferase 3A Gene Expression Regulation* Growth Differentiation Factor 5 / biosynthesis* Growth Differentiation Factor 5 / genetics Mice, Knockout Muscle, Skeletal / pathology Muscle, Skeletal / physiology* Regeneration* Satellite Cells, Skeletal Muscle / metabolism* Satellite Cells, Skeletal Muscle / pathology |
| IF | 4.966 |
| 引用数 | 9 |
| 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 | 12 |
| 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 | |
| 実験動物マウス | RBRC03731 |