論文 - 詳細
| RRC ID | 67767 |
|---|---|
| 著者 | Ozawa T, Morikawa M, Morishita Y, Ogikubo K, Itoh F, Koinuma D, Nygren PÅ, Miyazono K. |
| タイトル | Systemic administration of monovalent follistatin-like 3-Fc-fusion protein increases muscle mass in mice. |
| ジャーナル | iScience |
| Abstract |
Targeting the signaling pathway of growth differentiation factor 8 (GDF8), also known as myostatin, has been regarded as a promising strategy to increase muscle mass in the elderly and in patients. Accumulating evidence in animal models and clinical trials has indicated that a rational approach is to inhibit a limited number of transforming growth factor β (TGF-β) family ligands, including GDF8 and activin A, without affecting other members. Here, we focused on one of the endogenous antagonists against TGF-β family ligands, follistatin-like 3 (FSTL3), which mainly binds and neutralizes activins, GDF8, and GDF11. Although bivalent human FSTL3 Fc-fusion protein was rapidly cleared from mouse circulation similar to follistatin (FST)-Fc, monovalent FSTL3-Fc (mono-FSTL3-Fc) generated with the knobs-into-holes technology exhibited longer serum half-life. Systemic administration of mono-FSTL3-Fc in mice induced muscle fiber hypertrophy and increased muscle mass in vivo. Our results indicate that the monovalent FSTL3-based therapy overcomes the difficulties of current anti-GDF8 therapies. |
| 巻・号 | 24(5) |
| ページ | 102488 |
| 公開日 | 2021-5-21 |
| DOI | 10.1016/j.isci.2021.102488 |
| PII | S2589-0042(21)00456-9 |
| PMID | 34113826 |
| PMC | PMC8170004 |
| IF | 4.447 |
| 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 | 2 |
| 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 | |
| 遺伝子材料 | CSII-CA-MCS-IRES-Puro (RDB19592) CSII-CA-MCS-IRES-Hyg (RDB19593) CSII-EF-RfA (RDB04387) |