論文 - 詳細
| RRC ID | 57977 |
|---|---|
| 著者 | Onodera Y, Teramura T, Takehara T, Fukuda K. |
| タイトル | Transforming Growth Factor β-Activated Kinase 1 Regulates Mesenchymal Stem Cell Proliferation Through Stabilization of Yap1/Taz Proteins. |
| ジャーナル | Stem Cells |
| Abstract |
Bone marrow-derived mesenchymal stem cells (BMMSCs) are multipotent stem cells capable of differentiation into a variety of cell types, proliferation, and production of clinically useful secretory factors. These advantages make BMMSCs highly useful for cell transplantation therapy. However, the molecular network underlying BMMSC proliferation remains poorly understood. Here, we showed that TGFβ-activated kinase 1 (Tak1) is a critical molecule that regulates the activation of cell cycling and that Tak1 inhibition leads to quiescence in BMMSCs both in vivo and in vitro. Mechanistically, Tak1 was phosphorylated by growth factor stimulations, allowing it to bind and stabilize Yap1/Taz, which could then be localized to the nucleus. We also demonstrated that the quiescence induction by inhibiting Tak1 increased oxidized stress tolerance and improved BMMSC engraftment in intramuscular and intrabone marrow cell transplantation models. This study reveals a novel pathway controlling BMMSC proliferation and suggests a useful method to improve the therapeutic effect of BMMSC transplantation. Stem Cells 2019;37:1595-1605. |
| 巻・号 | 37(12) |
| ページ | 1595-1605 |
| 公開日 | 2019-12-1 |
| DOI | 10.1002/stem.3083 |
| PMID | 31461199 |
| PMC | PMC6916189 |
| MeSH | Adaptor Proteins, Signal Transducing / metabolism* Animals Bone Marrow Cells / cytology Cell Cycle Proteins / metabolism* Cell Differentiation / physiology Cell Proliferation / physiology Cells, Cultured Humans MAP Kinase Kinase Kinases / genetics MAP Kinase Kinase Kinases / metabolism* Male Mesenchymal Stem Cell Transplantation Mesenchymal Stem Cells / cytology Mesenchymal Stem Cells / physiology* Mice Mice, Inbred C57BL Phosphorylation Regeneration / physiology Trans-Activators / metabolism* YAP-Signaling Proteins |
| 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 | 9 |
| 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 | Bone marrow-derived mesenchymal stem cells |