| Project/Area Number |
17K17919
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Integrative animal science
General physiology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
Sakai Yusuke 山口大学, 共同獣医学部, 助教 (60615722)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | USP15 / 細胞内シグナル伝達 / 生殖器 / 脂質代謝 / 雌性生殖器 / 生理学 / 細胞・組織 |
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| Outline of Final Research Achievements |
Immunohistochemistry on uterus and ovary of wild type mice revealed that USP15 is expressed in luteal cells and uterine epithelial cells in accordance with lipid accumulation in these cells. In vitro assays using endometrial cell line showed progesterone, not estradiol, induced expression of USP15 and lipid accumulation. These results suggest USP15 promote lipid accumulation under progesterone stimuli. However, the mechanism of USP15-promoted lipid accumulation is still unclear and further analysis are required.
We also investigated the role of USP15 other than lipid metabolism. In this study, scratch assay using endometrial cell line and its USP15-knockout strain was performed. Results demonstrate that USP15 promote cell motility under HGF stimulation. In USP15-knockout cell line expression level of phosphorylated c-Cbl was decreased in comparison with wild type cell line. These results suggest USP15 inhibit degradation of c-Cbl and enhance HGF signal transduction.
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| Academic Significance and Societal Importance of the Research Achievements |
HGFシグナル伝達は子宮内膜腺癌の浸潤性や増殖活性の増強に関わるとされている。本研究からUSP15はHGFシグナル伝達経路を促進することがわかったため、子宮内膜腺癌の治療としてUSP15を標的とする抗癌戦略の根拠の1つとなり得る。
子宮や卵巣における脂質蓄積の意義については不明な点が多いが、USP15欠損マウスでは黄体組織がやや萎縮性であったことから、USP15が脂質代謝を通して生殖周期の恒常性の維持に関与している可能性が推測された。脂質代謝異常は不妊の原因の1つとして知られており、生殖器の恒常性と脂質代謝の関連性を調べることは重要であり、本研究はその一端を担うものと考えられた。
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