| Project/Area Number |
17H04043
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General medical chemistry
|
|---|
| Research Institution | Yamaguchi University |
|---|
Principal Investigator |
SEIKI Makoto 山口大学, 大学院医学系研究科, 教授 (50226619)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
浅岡 洋一 山口大学, 大学院医学系研究科, 講師 (10436644)
北川 孝雄 山口大学, 大学院医学系研究科, 助教(特命) (20614928)
古元 礼子 山口大学, 大学院医学系研究科, 講師 (70311818)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
|
|---|
| Keywords | YAP / メカノホメオスターシス / 臓器 / 力学制御 / 細胞外基質 / 発生医学 |
|---|
| Outline of Final Research Achievements |
Organs are three-dimensional (3D) but the presence of its underlying mechanism was not expected. We identified for the first time the mechanism by which YAP, a transcription co-activator,is essential for generating 3D organs withstanding gravity. We thus proposed that YAP is essential for the mechano-homeostasis in which bidirectional force mediated control between cell and its extracellular matrix (ECM) mediates cell proliferation and differentiation. In this study, we first uncovered the molecular network of YAP mediated mechano-homeostasis by the BioID approach. We also revealed that YAP is required in mesenchymal stem cells for generating 3D organs. Finally, we showed the potential mechanism causing tissue fibrosis and cell proliferation abnormalities by overexpression of CSPG4 identified by the BioID approach.
|
| Academic Significance and Societal Importance of the Research Achievements |
これまで細胞や組織レベルでの力学制御の解析は行われてきたが、臓器レベルでの力学制御については不明な点が多かった。特に、細胞と細胞外基質間の双方向性の力学制御を司る遺伝子は知られていなかった。本研究により明らかにしたYAPによるメカノホメオスターシス制御の分子機構の解明は、iPS/ES細胞から、より生体機能に近く、かつ治療に使える大きな3次元臓器を作るのに役立つ知見である。また、間葉系細胞でのYAPの働きの異常により、臓器が硬化する肝硬変などの繊維化疾患やがん発症につながる分子メカニズムの同定は、これらの難治性疾患の治療薬の開発に役立つと考えられる。
|
